ABSTRACT
Background and Objectives: High-grade malignant neuroendocrine tumors (G3 NETs) and neuroendocrine carcinomas (NECs) are characterized by rapid proliferation, high metastatic capacity, and strong expression of somatostatin receptors (SSTRs). We aimed to analyze the presence of SSTRs in NET G3 and NEC, and to correlate their expression with the use of octreotide and pasireotide. Materials and Methods: For this purpose, we first performed a retrospective study of G3 NET and NEC patients, which included the determination of SSTR expression and response to octreotide treatment. Second, we selected the H69 small cell lung cancer cell line to determine the effect of octreotide and pasireotide. Results: Our results showed the traditional somatostatin analog (SSA) octreotide was ineffective in patients with NET G3 and NEC. On the other hand, RT-qPCR showed a high expression of SSTR2 and SSTR5 in H69 cells. Interestingly, while octreotide did not modify H69 cell proliferation, a strong inhibition of proliferation was detected with the use of pasireotide. Conclusions: In view of these results, a clinical trial in NET G3 and NEC patients using pasireotide is necessary to determine the usefulness of this drug in improving patient treatment.
Subject(s)
Neuroendocrine Tumors , Octreotide , Receptors, Somatostatin , Somatostatin , Humans , Octreotide/therapeutic use , Octreotide/pharmacology , Somatostatin/analogs & derivatives , Somatostatin/therapeutic use , Somatostatin/pharmacology , Neuroendocrine Tumors/drug therapy , Receptors, Somatostatin/analysis , Retrospective Studies , Male , Middle Aged , Female , Aged , Cell Line, Tumor , Cell Proliferation/drug effects , Adult , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacologyABSTRACT
The chorioallantoic membrane (CAM) model, generated during avian development, can be used in cancer research as an alternative in vivo model to perform tumorigenesis in ovo due to advantages such as simplicity, low cost, rapid growth, and being naturally immunodeficient. The aim of this systematic review has been to compile and analyze all studies that use the CAM assay as a tumor induction model. For that, a systematic search was carried out in four different databases: PubMed, Scopus, Cochrane, and WOS. After eliminating duplicates and following the established inclusion and exclusion criteria, a total of 74 articles were included. Of these, 62% use the in ovo technique, 13% use the ex ovo technique, 9% study the formation of metastasis, and 16% induce tumors from patient biopsies. Regarding the methodology followed, the main species used is chicken (95%), although some studies use quail eggs (4%), and one article uses ostrich eggs. Therefore, the CAM assay is a revolutionary technique that allows a simple and effective way to induce tumors, test the effectiveness of treatments, carry out metastasis studies, perform biopsy grafts of patients, and carry out personalized medicine. However, unification of the methodology used is necessary.
Subject(s)
Neoplasms, Experimental , Animals , Chick Embryo , Humans , Biological Assay , Chorioallantoic Membrane , Precision MedicineSubject(s)
Dissection , Vena Cava, Inferior , Humans , Vena Cava, Inferior/surgery , Retroperitoneal Space , AbdomenABSTRACT
BACKGROUND: Liposomal Doxorubicin (Doxil®) was one of the first nanoformulations approved for the treatment of solid tumors. Although there is already extensive experience in its use for different tumors, there is currently no grouped evidence of its therapeutic benefits in non-small cell lung cancer (NSCLC). A systematic review of the literature was performed on the therapeutic effectiveness and benefits of Liposomal Doxil® in NSCLC. METHODS: A total of 1022 articles were identified in publications up to 2020 (MEDLINE, Cochrane, Web of Science Core Collection and Scopus). After applying inclusion criteria, the number was restricted to 114, of which 48 assays, including in vitro (n=20) and in vivo (animals, n=35 and humans, n=6) studies, were selected. RESULTS: The maximum inhibitory concentration (IC50), tumor growth inhibition rate, response and survival rates were the main indices for evaluating the efficacy and effectiveness of Liposomal DOX. These have shown clear benefits both in vitro and in vivo, improving the IC50 of free DOX or untargeted liposomes, depending on their size, administration, or targeting. CONCLUSION: Doxil® significantly reduced cellular proliferation in vitro and improved survival in vivo in both experimental animals and NSCLC patients, demonstrating optimal safety and pharmacokinetic behavior indices. Although our systematic review supports its benefits for the treatment of NSCLC, additional clinical trials with larger sample sizes are necessary to obtain more precise clinical data on its activity and effects in humans.
Subject(s)
Antibiotics, Antineoplastic , Carcinoma, Non-Small-Cell Lung , Doxorubicin , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Doxorubicin/analogs & derivatives , Doxorubicin/pharmacology , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Lung Neoplasms/drug therapy , Humans , Animals , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/therapeutic use , Polyethylene Glycols/chemistry , Cell Proliferation/drug effects , LiposomesABSTRACT
SUMMARY: Telocytes are a cell population described in 2011 with a multitude of functions such as tissue support, regulation of stem cell niches or intercellular signal transmission. However, there are no studies about their embryonic origin, their function in development, or their moment of appearance. The objective of this work is to try to answer these questions through histological and immunofluorescence studies with samples from the embryological collection of the Department of Anatomy of the University of Granada. In the results obtained, as demonstrated by immunofluorescence for CD34, the presence of these cells can be seen in the fourth week of embryonic development in the perinotochordal region. Its presence is evident from the sixth week of development in a multitude of organs such as the heart, skeletal muscle tissue and supporting tissue of various organs such as the kidney, brain or pericardium. Its function seems to be when the embryonic histological images are analyzed in an evolutionary way, to act as a scaffold or scaffold for the subsequent population by mature tissue elements. In conclusion, telocytes appear at a very early stage of embryonic development and would have a fundamental role in it as scaffolding and directors of organ and tissue growth.
Los telocitos son una población celular descrita en 2011 con multitud de funciones como el sostén tisular, la regulación de los nichos de células madre o la transmisión de señales intercelulares. Sin embargo, no existen estudios acerca del origen embrionario de los mismos, su función en el desarrollo ni su momento de aparición. El objetivo de este trabajo es tratar de responder a estos interrogantes mediante estudios histológicos y por inmunofluorescencia con muestras de la colección embriológica del Departamento de Anatomía de la Universidad de Granada. En los resultados se puede observar como se demuestra mediante inmunofluorescencia para CD34, la presencia de estas células en la cuarta semana del desarrollo embrionario en la región perinotocordal. Su presencia se evidencia a partir de la sexta semana del desarrollo en multitud de órganos como corazón, tejidos músculo esqueléticos y tejidos de sostén de diversos órganos como riñón, encéfalo o pericardio. Su función parece ser al ser analizadas las imágenes histológicas embrionarias de forma evolutiva, la de actuar como un andamiaje o scafold para el posterior poblamiento por elementos tisulares maduros. Como conclusión, los telocitos aparecen en un momento muy precoz del desarrollo embrionario y presentarían una función fundamental en el mismo como andamiajes y directores del crecimiento de los órganos y tejidos.
Subject(s)
Humans , Telocytes/metabolism , Telocytes/ultrastructure , Fluorescent Antibody Technique , Antigens, CD34ABSTRACT
Anemonia sulcata may be a source of marine natural products (MNPs) due to the antioxidant and antitumor activity of its crude homogenates shown in vitro in colon cancer cells. A bioguided chromatographic fractionation assay of crude Anemonia sulcata homogenates with and without its symbiont Symbiodinium was performed to characterize their bioactive composition and further determine their biological potential for the management of colorectal cancer (CRC). The 20% fractions retained the in vitro antioxidant activity previously reported for homogenates. As such, activation of antioxidant and detoxifying enzymes was also evaluated. The 40% fractions showed the greatest antiproliferative activity in T84 cells, synergistic effects with 5-fluoruracil and oxaliplatin, overexpression of apoptosis-related proteins, cytotoxicity on tumorspheres, and antiangiogenic activity. The predominantly polar lipids and toxins tentatively identified in the 20% and 40% fractions could be related to their biological activity in colon cancer cells although further characterizations of the active fractions are necessary to isolate and purify the bioactive compounds.
Subject(s)
Colorectal Neoplasms , Sea Anemones , Animals , Humans , Antioxidants/pharmacology , Antioxidants/metabolism , Chromatography , Colorectal Neoplasms/drug therapyABSTRACT
Sarcomas are a diverse group of neoplasms with an incidence rate of 15% of childhood cancers. They exhibit a high tendency to develop early metastases and are often resistant to available treatments, resulting in poor prognosis and survival. In this context, cancer stem cells (CSCs) have been implicated in recurrence, metastasis, and drug resistance, making the search for diagnostic and prognostic biomarkers of the disease crucial. The objective of this systematic review was to analyze the expression of CSC biomarkers both after isolation from in vitro cell lines and from the complete cell population of patient tumor samples. A total of 228 publications from January 2011 to June 2021 was retrieved from different databases, of which 35 articles were included for analysis. The studies demonstrated significant heterogeneity in both the markers detected and the CSC isolation techniques used. ALDH was identified as a common marker in various types of sarcomas. In conclusion, the identification of CSC markers in sarcomas may facilitate the development of personalized medicine and improve treatment outcomes.
ABSTRACT
Legumes are a highly nutritious source of plant protein, fiber, minerals and vitamins. However, they also contain several bioactive compounds with significant potential benefits for human health. The objectives of this study were to evaluate the antioxidant, antitumor and chemopreventive activity of functional extracts from legumes using raw and germinated flours of six legume species of commercial interest. The methodology carried out consisted on the development of protein hydrolysates, assessment of their antioxidant capacity and in vitro tests on T84, HCT15 and SW480 colorectal cancer (CRC) cell lines. Our results showed a high antitumor activity of protein hydrolysate from M. sativa. Likewise, when combined with 5-Fluorouracile (5-Fu), there was a synergistic effect using extract concentrations from 50 to 175 µg/mL and 5-Fu concentrations from 1.5 to 5 µM. Similarly, the induction effect on detoxifying enzymes by the extracts of M. sativa, germinated V. faba Baraca × LVzt1 and V. narbonensis, which produced a higher induction rate than the positive control sulforaphane (10 µM), should be highlighted. Therefore, incorporating these enzymes into the diet could provide nutritional effects, as well as play an effective role in cancer chemoprevention and therapy.
ABSTRACT
Breast cancer is the most common type of cancer in women, with chemotherapy being the main strategy. However, its effectiveness is reduced by drug resistance mechanisms. miR-21 is upregulated in breast cancer that has been linked to drug resistance and carcinogenic processes. Our aim was to capture miR-21 with a circular sponge (Circ-21) and thus inhibit the carcinogenic processes and drug resistance mechanisms in which it participates. Proliferation, migration, colony formation, cell cycle, and poly [ADP-ribose] polymerase 1 (PARP-1) and vascular endothelial growth factor (VEGF) detection assays were performed with MCF7 breast cancer cells and MCF10A non-tumor cells. In addition, doxorubicin resistance tests and detection of drug resistance gene expression were performed in MCF7 cells. Reduction in proliferation, as well as migration and colony formation, increased PARP-1 expression, inhibition of VEGF expression and cell cycle arrest in G2/M phase were displayed in the Circ-21 MCF7, which were not observed in the MCF10A cells. Furthermore, in the MCF7 cells, the Circ-21 enhanced the antitumor activity of doxorubicin and decreased the expression of resistance genes: ABCA1, ABCC4, and ABCC5. Based on these results, the use of Circ-21 can be considered a first step for the establishment of an effective gene therapy in the treatment of breast cancer.
Subject(s)
Breast Neoplasms , MicroRNAs , Female , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Vascular Endothelial Growth Factor A/metabolism , Gene Expression Regulation, Neoplastic , MicroRNAs/therapeutic use , Cell Line, Tumor , Cell Proliferation , Doxorubicin/pharmacology , Doxorubicin/therapeutic useABSTRACT
Glioblastoma multiforme is the most common malignant primary brain tumor in adults. Despite new treatments developed including immunomodulation using vaccines and cell therapies, mortality remains high due to the resistance mechanisms presented by these tumor cells and the function of the blood-brain barrier that prevents the entry of most drugs. In this context of searching for new glioblastoma therapies, the study of the existing drugs to treat neurological disorder is gaining great relevance. The aim of this study was to determine, through a preliminary in vitro study on human glioblastoma (A172, LN229), anaplastic glioma (SF268) and neuroblastoma (SK-N-SH) cell lines, the possible antitumor activity of the active principles of several drugs (levomepromazine, haloperidol, lacosamide, valproic acid, levetiracetam, glatiramer acetate, fingolimod, biperiden and dextromethorphan) with the ability to cross the blood-brain barrier and that are commonly used in neurological disorders. Results showed that levetiracetam, valproic acid, and haloperidol were able to induce a relevant synergistic antitumor effect when associated with the chemotherapy currently used in clinic (temozolomide). Regarding the mechanism of action, haloperidol, valproic acid and levomepromazine caused cell death by apoptosis, while biperiden and dextromethorphan induced autophagy. Fingolimod appeared to have anoikis-related cell death. Thus, the assayed drugs which are able to cross the blood-brain barrier could represent a possibility to improve the treatment of neural tumors, though future in vivo studies and clinical trials will be necessary to validate it.
Subject(s)
Brain Neoplasms , Glioblastoma , Adult , Humans , Glioblastoma/drug therapy , Glioblastoma/pathology , Valproic Acid , Levetiracetam/pharmacology , Methotrimeprazine/pharmacology , Methotrimeprazine/therapeutic use , Haloperidol , Biperiden/pharmacology , Biperiden/therapeutic use , Dextromethorphan/pharmacology , Dextromethorphan/therapeutic use , Fingolimod Hydrochloride , Brain Neoplasms/drug therapy , Cell Line, Tumor , ApoptosisABSTRACT
The emergence of resistance to pancreatic cancer (PC) current treatment requires the development of new therapeutic strategies. In this context, bioactive molecules from plant extracts have shown excellent properties to improve classical therapy against this type of tumor. This systematic review aims to collect all the in vitro studies related to the antiproliferative activity of isolated plant molecules that support their applicability in PC. A total of 620 articles published in the last 10 years were identified, although only 28 were finally included to meet the inclusion criteria. Our results reflect the most important biomolecules from natural compounds that induce cell death in PC and their essential mechanism of cell death, including apoptosis, pathways activated by the KRAS mutation and cycle cell arrest, among others. These in vitro studies provide an excellent molecule guide showing applications against PC and that should be tested in vivo and in clinical trials to determine their usefulness to reduce PC incidence and to improve the prognosis of these patients. However, natural compounds are isolated in small amounts, which prevents comprehensive drug screening, being necessary the role of organic synthesis for the total synthesis of natural compounds or for the synthesis of their simplified and bioactive analogs.
ABSTRACT
The failure of chemotherapeutic treatment in colorectal cancer (CRC), the second most mortal cancer worldwide, is associated with several drug limitations, such as non-selective distribution, short half-life, and development of multiple resistances. One of the most promising strategies in CRC therapy is the development of delivery systems based on nanomaterials that can transport antitumor agents to the tumor site more efficiently, increasing accumulation within the tumor and thus the antitumor effect. In addition to taking advantage of the increased permeability and retention effect (EPR) of solid tumors, these nanoformulations can be conjugated with monoclonal antibodies that recognize molecular markers that are specifically over-expressed on CRC cells. Active targeting of nanoformulations reduces the adverse effects associated with the cytotoxic activity of drugs in healthy tissues, which will be of interest for improving the quality of life of cancer patients in the future. This review focuses on in vitro and in vivo studies of drug delivery nanoformulations functionalized with monoclonal antibodies for targeted therapy of CRC.
Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Humans , Quality of Life , Drug Delivery Systems , Antineoplastic Agents/pharmacology , Antibodies, Monoclonal/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathologyABSTRACT
Amorphous calcium phosphate nanoparticles (ACP NPs) exhibit excellent biocompatibility and biodegradability properties. ACP NPs were functionalized with two coumarin compounds (esculetin and euphorbetin) extracted from Euphorbia lathyris seeds (BC-ACP NPs) showing high loading capacity (0.03% and 0.34% (w/w) for esculetin and euphorbetin, respectively) and adsorption efficiency (2.6% and 33.5%, respectively). BC-ACP NPs, no toxic to human blood cells, showed a more selective cytotoxicity against colorectal cancer (CRC) cells (T-84 cells) (IC50, 71.42 µg/ml) compared to non-tumor (CCD18) cells (IC50, 420.77 µg/ml). Both, the inhibition of carbonic anhydrase and autophagic cell death appeared to be involved in their action mechanism. Interestingly, in vivo treatment with BC-ACPs NPs using two different models of CRC induction showed a significant reduction in tumor volume (62%) and a significant decrease in the number and size of polyps. A poor development of tumor vasculature and invasion of normal tissue were also observed. Moreover, treatment increased the bacterial population of Akkermansia by restoring antioxidant systems in the colonic mucosa of mice. These results show a promising pathway to design innovative and more efficient therapies against CRC based on biomimetic calcium phosphate NPs loaded with natural products.
Subject(s)
Biological Products , Carbonic Anhydrases , Colonic Neoplasms , Euphorbia , Nanoparticles , Humans , Mice , Animals , Antioxidants , Colonic Neoplasms/drug therapy , Coumarins , Calcium PhosphatesABSTRACT
Pancreatic cancer (PC) is one of the tumors with the lowest survival rates due to the poor efficacy of the treatments currently used. Gemcitabine (GMZ), one of the chemotherapeutic agents employed when the tumor is unresectable, frequently fails due to the development of drug resistance. PARP1 is a relevant protein in this phenomenon and appears to be related to cancer progression in several types of tumors, including PC. To determine the relevance of PARP1 in the development and treatment of PC, we used the Panc02 cell line to generate modified PC cells with stably inhibited PARP1 expression (Panc02-L) and used GMZ, Olaparib (OLA) and GMZ+OLA as therapeutic strategies. Viability, radiosensitization, angiogenesis, migration, colony formation, TUNEL, cell cycle, multicellular tumorsphere induction and in vivo assays were performed to test the influence of PARP1 inhibition on resistance phenomena and tumor progression. We demonstrated that stable inhibition or pharmacological blockade of PARP1 using OLA-sensitized Panc02 cells against GMZ significantly decreased their IC50, reducing colony formation capacity, cell migration and vessel formation (angiogenesis) in vitro. Furthermore, in vivo analyses revealed that Panc02-L-derived (PARP1-inhibited) tumors showed less growth and lethality, and that GMZ+OLA treatment significantly reduced tumor growth. In conclusion, PARP1 inhibition, both alone and in combination with GMZ, enhances the effectiveness of this chemotherapeutic agent and represents a promising strategy for the treatment of PC.
Subject(s)
Antineoplastic Agents , Pancreatic Neoplasms , Humans , Xenograft Model Antitumor Assays , Cell Line, Tumor , Poly (ADP-Ribose) Polymerase-1 , Pancreatic Neoplasms/pathology , Antineoplastic Agents/pharmacology , Gemcitabine , Pancreatic NeoplasmsABSTRACT
Continuous improvements in morphological and histochemical analyses of Apis mellifera could improve our understanding of the anatomy and physiology of these insects at both the cellular and tissue level. In this work, two different approaches have been performed to add new data on the abdomen of worker bees: (i) Micro-computed tomography (Micro-CT), which allows the identification of small-scale structures (micrometers) with adequate/optimal resolution and avoids sample damage and, (ii) histochemical multi-staining with Periodic Acid-Schiff-Alcian blue, Lactophenol-Saphranin O and pentachrome staining to precisely characterize the histological structures of the midgut and hindgut. Micro-CT allowed high-resolution imaging of anatomical structures of the honeybee abdomen with particular emphasis on the proventriculus and pyloric valves, as well as the connection of the sting apparatus with the terminal abdominal ganglia. Furthermore, the histochemical analyses have allowed for the first-time description of ventricular telocytes in honeybees, a cell type located underneath the midgut epithelium characterized by thin and long cytoplasmic projections called telopodes. Overall, the analysis of these images could help the detailed anatomical description of the cryptic structures of honeybees and also the characterization of changes due to abiotic or biotic stress conditions.
ABSTRACT
Basil is an aromatic herb with a high concentration of bioactive compounds. The oil extracted from its seeds is a good source of α-linolenic acid (ALA) and also provides substantial amounts of linoleic acid (LA). This study aimed to test the bioavailability of the oil derived from basil seeds and its effects on different physiological parameters using 7-15% dietary inclusion levels. Furthermore, the assimilation of LA and ALA and their transformation in long-chain polyunsaturated fatty acids (LC-PUFAs) have been studied. Digestive utilization of total fat from basil seed oil (BSO) was high and similar to that of olive oil used as a control. Consumption of BSO resulted in increased LA and ALA levels of the plasma, liver, and erythrocyte membrane. In addition, the transformation of LA to arachidonic acid (ARA) was decreased by the high dietary intake of ALA which redirected the pathway of the Δ-6 desaturase enzyme towards the transformation of ALA into eicosapentaenoic acid (EPA). No alterations of hematological and plasma biochemical parameters were found for the 7 and 10% dietary inclusion levels of BSO, whereas a decrease in the platelet count and an increase in total- and HDL-cholesterol as well as plasma alkaline phosphatase (ALP) were found for a 15% BSO dose. In conclusion, BSO is a good source of ALA to be transformed into EPA and decrease the precursor of the pro-inflammatory molecule ARA. This effect on the levels of EPA in different tissues offers potential for its use as a dietary supplement, novel functional food, or a constituent of nutraceutical formulations to treat different pathologies.
Subject(s)
Fatty Acids, Omega-3 , Ocimum basilicum , Animals , Arachidonic Acid/analysis , Biological Availability , Biotransformation , Eicosapentaenoic Acid/analysis , Fatty Acids/analysis , Fatty Acids, Omega-3/chemistry , Linoleic Acid/analysis , Models, Theoretical , Plant Oils/chemistry , Rats , Seeds/chemistry , alpha-Linolenic Acid/metabolismABSTRACT
Nannochloropsis gaditana is a microalga with interesting nutritional and functional value due to its high content of protein, polyunsaturated fatty acids, and bioactive compounds. However, the hardness of its cell wall prevents accessibility to these components. This work aimed to study the effect of a treatment to increase the fragility of the cell wall on the bioavailability of its nutrients and functional compounds. The antioxidant and antiproliferative capacity of functional extracts from treated and untreated N. gaditana was assessed, and the profile of bioactive compounds was characterized. Furthermore, to study the effect of treatment on its nutrient availability and functional capacity, an in vivo experiment was carried out using a rat experimental model and a 20% dietary inclusion level of microalgae. Functional extracts from treated N. gaditana exhibited higher antioxidant activity than the untreated control. Furthermore, the treated microalga induced hypoglycemic action, higher nitrogen digestibility, and increased hepatic antioxidant activity. In conclusion, N. gaditana has interesting hepatoprotective, antioxidant, and anti-inflammatory potential, thus proving itself an ideal functional food candidate, especially if the microalga is treated to increase the fragility of its cell wall before consumption.
Subject(s)
Microalgae , Stramenopiles , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Microalgae/metabolism , Nutrition Assessment , Rats , Stramenopiles/metabolismABSTRACT
The emergence of adverse effects and resistance to colorectal cancer (CRC) current therapies calls for the development of new strategies aimed at both preventing and treating. In this context, functional extracts from Brassicaceae family contains abundant bioactive compounds directly related to a positive effect on human health including cancer. The main objective of this systematic review is to compile all recent studies that analyzed the in vitro antiproliferative activity of functional extracts or isolated molecules from the Brassicaceae family against CRC. A total of 711 articles published between January 2011 and May 2021 were identified. Of them, 68 met our inclusion criteria. Different standardized protocols using variable parts of plants of the Brassicaceae family resulted in diverse bioactive extracts and/or compounds. Most of them were related to isothiocyanates, which showed significant antitumor activity against CRC. These in vitro studies provide an excellent guide to direct research on the applications of plants of the Brassicaceae family to the prevention of this type of tumor. The extracts and molecules with demonstrated activity against CRC should be tested in vivo and in clinical trials to determine their usefulness in the prevention of this cancer to reduce its global incidence.
Subject(s)
Brassicaceae , Colonic Neoplasms , Colonic Neoplasms/prevention & control , Humans , Plant ExtractsABSTRACT
Lung cancer is the most common cancer in the world and several miRNAs are associated with it. MiRNA sponges are presented as tools to inhibit miRNAs. We designed a system to capture miRNAs based on circular RNAs (circRNA). To demonstrate its usefulness, we chose miR-21, which is upregulated and implicated in lung cancer. We constructed a miR-21 sponge and inserted it into a vector that facilitates circular RNA production (Circ-21) to study its effect on growth, colony formation, and migration in lung cancer cell lines and multicellular tumor spheroids (MTS). Circ-21 induced a significant and time-dependent decrease in the growth of A549 and LL2 cells, but not in L132 cells. Furthermore, A549 and LL2 cells transfected with Circ-21 showed a lower number of colonies and migration than L132. Similar findings were seen in A549 and LL2 Circ-21 MTS, which showed a significant decrease in volume growth, but not in L132 Circ-21 MTS. Based on this, the miR-21 circular sponge may suppress the processes of tumorigenesis and progression. Therefore, our system based on circular sponges seems to be effective, as a tool for the capture of other miRNAs.
Subject(s)
Lung Neoplasms , MicroRNAs , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/therapy , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/geneticsABSTRACT
Introduction: Pancreatic cancer treatment in advanced stages is based on different chemotherapy regimens. Cancer stem cells are responsible for tumor chemoresistance and recurrence in adjuvant and metastatic settings. The objective of this article was to evaluate how these chemotherapeutic regimens affect the proportion of cancer stem cells and the expression of stemness markers. Method: We used the pancreatic adenocarcinoma cell line PANC-1 as a model to apply different chemotherapeutic protocols (monotherapy and combined therapy) using 5-Fluorouracil, Oxaliplatin, Irinotecan, Gemcitabine and Abraxane. Results: After analyzing different tumor stem cell markers (SOX2, OCT4, CD133, CD44 and CD24) in pancreatic cancer cells treated with different chemotherapeutic protocols by means of RT-qPCR, Oxaliplatin and Gemcitabine in monotherapy were the chemotherapies that selected the most cancer stem cells while the FOLFIRI protocol decreased them. Conclusions: Regarding the selection of markers, it has been much higher in the case of Gemcitabine alone. In conclusion, these findings could improve and personalize pancreatic cancer therapy. (AU)
Introducción: El tratamiento del cáncer de páncreas en estadios avanzados se basa en diferentes regímenes de quimioterapia. Las células madre cancerosas son responsables de la quimiorresistencia tumoral y la recurrencia tras tratamientos en etapa adyuvante y metastásica. El objetivo de este artículo fue evaluar cómo estos regímenes quimioterapéuticos afectan a la proporción de células madre cancerosas y la expresión de sus marcadores. Método: Utilizamos la línea celular de adenocarcinoma pancreático PANC-1 como modelo para aplicar diferentes protocolos quimioterapéuticos (monoterapia y terapia combinada) utilizando 5-Fluorouracilo, Oxaliplatino, Irinotecán, Gemcitabina y Abraxane. Resultados: Tras analizar mediante RT-qPCR diferentes marcadores de células madre tumorales (SOX2, OCT4, CD133, CD44 y CD24) en células de cáncer de páncreas tratadas con diferentes protocolos quimioterapéuticos, el Oxaliplatino y la Gemcitabina en monoterapia fueron los quimioterápicos que seleccionaron en mayor medida las células madre cancerosas mientras que el protocolo FOLFIRI las disminuyó. Conclusiones: En cuanto a la selección de marcadores, ha sido mucho mayor en el caso de Gemcitabina en monoterapia. En conclusión, estos hallazgos podrían mejorar y personalizar la terapia del cáncer de páncreas. (AU)