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1.
Braz. j. med. biol. res ; 56: e12638, 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1447691

ABSTRACT

RNA interference (RNAi) treatment has been proven to be an important therapeutic approach in cancer based on downregulation of target-oncogenes, but its clinical efficacy still needs further investigation. LMP1 is usually presented by Epstein-Barr virus (EBV)-positive tumor cells like EBV-associated nasopharyngeal carcinoma (NPC) and acts as an oncogene in tumorigenesis. However, the mechanism of LMP1 as a proto-oncogene in nasopharyngeal carcinoma is still unclear. Two sequence-specific shRNAs 1 and 2 were designed to target the different nucleotide loci of EBV latent antigen LMP1 gene and a series of in vivo and in vitro experiments were performed to investigate the therapeutic effect of sequence-specific shRNAs targeting LMP1 and its related molecular mechanisms in EBV-positive NPC. LMP1-shRNA2 generated a truncated LMP1 mRNA and protein, whereas LMP1-shRNA1 completely blocked LMP1 mRNA and protein expression. Both LMP1-shRNAs inhibited the proliferation and migration of NPC cells overexpressing LMP1 (NPC-LMP1) as well as the NPC-associated myeloid-derived suppressor cell (MDSC) expansion in vitro. However, LMP1-shRNA2 maintained the immunogenicity of NPC-LMP1 cells, which provoked MHC-class I-dependent T cell recognition. LMP1-shRNAs inhibited tumor growth in nude mice but did not reach statistical significance compared to control groups, while the LDH nanoparticle loaded LMP1-shRNAs and the antigen-specific T cells induced by NPC-LMP1 cells treated with LMP1-shRNA2 significantly reduced tumor growth in vivo. LMP1-RNAi-based anti-tumor therapy could be a new hope for the clinical efficacy of RNAi treatment of tumors like NPC.

2.
Journal of Pharmaceutical Practice ; (6): 465-471, 2023.
Article in Chinese | WPRIM | ID: wpr-984554

ABSTRACT

Bavachinin is a dihydroflavone isolated from dried ripe fruits of Psoralea corylifolia L.,which has various pharmacological activities, such as anti-tumor, anti-virus, anti-diabetes, anti-inflammatory and neuroprotective, and good potential in clinical applications. With the increasing concern about the safety of P. corylifolia applications in clinical, the bavachinin has been found to be one of the main components causing liver injury. In this paper, the pharmacological activities and hepatotoxicity of bavachinin in the recent 20 years were reviewed, in order to provide reference for the further study and clinical application.

3.
Chinese Journal of Primary Medicine and Pharmacy ; (12): 2-6, 2023.
Article in Chinese | WPRIM | ID: wpr-991696

ABSTRACT

Objective:To analyze the related factors of neurotoxicity induced by oxaliplatin chemotherapy in patients with colorectal cancer and its prevention and treatment strategies.Methods:A total of 300 patients with colorectal cancer treated with oxaliplatin in Zhejiang Cancer Hospital from January 2018 to December 2020 were randomly selected for baseline collection using the convenience sampling method. The occurrence of oxaliplatin-induced peripheral neurotoxicity (OIPN) was statistically analyzed. The factors that affect the occurrence of OIPN were analyzed using univariate analysis.Results:There was a significant difference in OIPN score between patients of different genders, between patients who had different education levels, between patients who had different occupations, and between patients who lived in different long-term residence places ( t = 7.29, 3.39, 2.53, 18.11, all P < 0.05). There was no significant difference in OIPN score between patients adhering to different religion's beliefs, between patients married and not, between patients who lived with and without members, between patients who paid medical costs and not, and between patients who had a previous history of smoking and not ( t = 3.25, 0.37, 0.69, 2.39, 0.15, all P > 0.05). There was a significant difference in OIPN score between patients with different tumor-node-metastasis stages, between patients who received medication via different administration routes, and between patients who received different times of oxaliplatin administration ( t = 8.40, 3.34, 3.49, all P < 0.05). Conclusion:Medical staff should pay attention to the occurrence of OIPN in patients with colorectal cancer treated with oxaliplatin, focus on the patient's factors related to the disease, and take correct and effective coping strategies promptly to reduce the adverse reactions, improve the quality of life, and ensure the therapeutic effect.

4.
Acta Pharmaceutica Sinica ; (12): 3539-3548, 2023.
Article in Chinese | WPRIM | ID: wpr-1004637

ABSTRACT

Cancer and cardiovascular diseases are the two major causes of death worldwide. The application of anti-tumor drugs has significantly improved the prognosis of patients, the cardiovascular toxicity caused by the application of them has become an important factor affecting the survival and prognosis of cancer patients. Therefore, the prevention and treatment of cardiovascular toxicity related to cancer treatment is increasingly important. The cardiovascular toxicity associated with anti-tumor drugs exhibits different clinical manifestations and involves multiple pathological mechanisms. This article reviews the current research progress from the perspective of the characteristics, molecular mechanisms and prevention and treatment strategies of cardiovascular toxicity caused by cancer drugs.

5.
Cancer Research on Prevention and Treatment ; (12): 1180-1184, 2023.
Article in Chinese | WPRIM | ID: wpr-1003797

ABSTRACT

Cholangiocarcinoma is a bile duct adenocarcinoma derived from the bile duct epithelium. Current treatment strategies for cholangiocarcinoma include surgery, chemotherapy, and radiotherapy. Surgical treatment is the first choice for all subtypes of cholangiocarcinoma. However, cholangiocarcinoma has the characteristics of high malignancy, easy recurrence after surgery, and low 5-year survival rates. Recent studies have found that many traditional Chinese medicines exhibit excellent anti-tumor effects in the treatment of various cancers, including cholangiocarcinoma. These medicines have advantages, such as low prices and abundant reserves, and are considered as an effective and safe complementary and alternative therapy for the treatment of cholangiocarcinoma. This article aims to review the effects of traditional Chinese medicine on cholangiocarcinoma from different aspects and levels in recent years. Results will provide new ideas for the prevention and treatment of cholangiocarcinoma.

6.
Acta Pharmaceutica Sinica ; (12): 2218-2225, 2023.
Article in Chinese | WPRIM | ID: wpr-999132

ABSTRACT

The most toxic DNA damage is DNA double strand breaks (DSBs), which are mainly repaired by non-homologous end joining (NHEJ). DNA-dependent protein kinase (DNA-PK) belongs to phosphatidylinositol-3-kinase-related protein kinase family (PIKK) and plays a key role in NHEJ. DNA-PK is overexpressed in a variety of cancer cells and is related to the occurrence, development and drug resistance of malignant tumors. In this article, the representative DNA-PK inhibitors with anticancer effects are reviewed, in order to provide a reference to discovery novel DNA-PK inhibitors.

7.
Acta Pharmaceutica Sinica ; (12): 3004-3015, 2023.
Article in Chinese | WPRIM | ID: wpr-999065

ABSTRACT

Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.

8.
Acta Pharmaceutica Sinica ; (12): 2952-2960, 2023.
Article in Chinese | WPRIM | ID: wpr-999057

ABSTRACT

Dihydrofolate reductase (DHFR) is a well-known key target in the treatment of tumors, bacterial infections, and parasitic infections; and it plays a critical role in the biosynthesis of cellular DNA. DHFR inhibitors interfere with one-carbon metabolism by inhibiting substrate binding to DHFR, thereby inhibiting cell proliferation. Research on DHFR inhibitors has continued since the 1940s. To date, a variety of DHFR inhibitors have come into the market, primarily used for anti-tumor, antibacterial, antiparasitic, and anti-inflammatory therapy. This review summarizes the research progress of DHFR inhibitors with antitumor or antibacterial effects in recent years based on the classification of single-target and dual-target and looks forward to the opportunities and challenges faced by the work in this field.

9.
Acta Pharmaceutica Sinica ; (12): 2970-2978, 2023.
Article in Chinese | WPRIM | ID: wpr-999039

ABSTRACT

Inositol requiring enzyme 1 alpha (IRE1α), a widespread transmembrane protein in mammals, is an endoplasmic reticulum stress (ER stress) receptor. Among the three signaling pathways of the unfolded protein response (UPR), the IRE1α pathway is the most conservative. And there is a growing body of evidence that the occurrence and development of tumors is closely related to the over-expression of IRE1α. Therefore, the study of the IRE1α inhibitors is of great significance to the discovery of new anti-tumor drugs and has been attracting more and more attention. In the hope of providing ideas for the research of targeting IRE1α for cancer therapy, this paper reviewed the data of representative IRE1α inhibitors, including inhibitory activity, the mechanism of action, structural characteristics, and so on.

10.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 213-219, 2023.
Article in Chinese | WPRIM | ID: wpr-996523

ABSTRACT

Malignant tumors are one of the main causes of human death worldwide and pose a serious threat to human health. The current treatment methods are mainly the combination of chemotherapeutics, surgery, radiotherapy, or hormone therapy. The treatment process has limitations such as multidrug resistance, non-selective targeting of cancer cells, and drug toxicity. With the development and application of traditional Chinese medicine (TCM), Chinese medicine has the characteristics of multi-angle and multi-mechanism coordination and slight toxic and side effects. It can effectively inhibit tumor proliferation, differentiation, and metastasis, and avoid drug resistance, serving as the focus of current tumor treatment research. Hedysari Radix, one of the genuine medicinal materials in Gansu province, is a tonic Chinese medicine with a wide range of pharmacological effects such as anti-inflammation, immune regulation, anti-oxidation, prevention and treatment of diabetic complications. In the majority of the ancient works on herbs of the past dynasties, Hedysari Radix was included under the item of Astragali Radix and used as Astragali Radix. Hedysari Radix is superior to Astragali Radix in enhancing immunity, scavenging free radicals, and resisting liver fibrosis. Studies have found that the effective components of Hedysari Radix have a prominent anti-tumor effect and a significant inhibitory effect on various malignant tumors such as liver cancer, bladder cancer, gastric cancer, breast cancer, and colorectal cancer. They can also combine with clinical anti-cancer drugs to reduce the toxic and side effects of chemotherapy drugs and improve the tolerance of patients during chemotherapy. On the basis of current research, this study summarized the mechanism of Hedysari Radix active components in inducing cell apoptosis, blocking cell cycle, inhibiting tumor cell proliferation, migration, and invasion, regulating micro mRNA (miRNA), inducing cell autophagy, enhancing immune regulation, as well as reducing toxicity and enhancing efficiency and sensitization with clinical chemotherapeutics, and systematically explained the anti-tumor mechanism of Hedysari Radix active components, aiming to provide a basic reference for the further exploration of the anti-tumor mechanism of Hedysari Radix and the further development and utilization of its effective components.

11.
Chinese Journal of Hospital Administration ; (12): 46-50, 2023.
Article in Chinese | WPRIM | ID: wpr-996033

ABSTRACT

In recent years, the rapid increase in cancer treatment costs in China had brought a huge economic burden to society, and it was urgent to standardize the rational application of anti-tumor drugs. In the context of the reform of group payment related to disease diagnosis, a tertiary first-class hospital focused on the needs of patients and guided by value-based healthcare, established a professional and normalized refined anti-tumor drug management system, setted up a multidisciplinary diagnosis and treatment team, and promoted " Internet plus pharmaceutical services" in December 2018.From 2019 to 2021, the proportion of hospital drugs were 30.8%, 30.1%, and 27.3%, respectively. The amount of money spent on anti-tumor drugs were 83.25 million yuan, 76.41 million yuan, and 62.48 million yuan, respectively, showing a decreasing trend year by year. The practice of refined management of anti-tumor drugs fully reflected the core concept of value based healthcare, achieving closed-loop management of the entire process of drugs, improving the level of rational drug use, reducing the economic burden on patients, and providing reference for improving the level of rational use of anti-tumor drugs in public hospitals.

12.
China Pharmacy ; (12): 648-652, 2023.
Article in Chinese | WPRIM | ID: wpr-965499

ABSTRACT

OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs, and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st, 2020 to July 1st, 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed, 257 (81.3%) had problems with the contents of informed consent form, mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer (68.5%), the incomplete notification of the test content (59.1%), the insufficient notification of rights and interests and risks (58.4%), the insufficient notification of personal information protection (56.0%), and the nonstandard expression of the informed consent form (52.5%). CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs (GCP). The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form, and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing, continue to strengthen the examination ability, improve the examination quality, and effectively protect the safety and interests of the subjects.

13.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 275-282, 2023.
Article in Chinese | WPRIM | ID: wpr-964969

ABSTRACT

Malignant tumor poses a threat to human health and life. The incidence and fatality rate of malignant tumor have been on the rise. The currently available therapies are radiotherapy and chemotherapy, which cause severe adverse reactions and irreversible damage and thus influence the quality of life of patients. Therefore, it is urgent to find new, safe and effective antitumor drugs. Chinese medicinals are safe with little adverse reactions and long-lasting effect in the treatment of tumor, which have attracted the attention of scholars. Amid the advancement of medical research, more and more anti-tumor components have been extracted from Chinese medicinals. Phellinus is a valuable Chinese medicinal material, and the chemical components mainly include polysaccharides, flavonoids, triterpenes, and polyphenols, which have anti-inflammatory, hypoglycemic, liver-protecting, and anti-tumor effect. The chemical components of Phellinus can inhibit various malignant tumors such as lung cancer, gastric cancer, colon cancer, and melanoma. It exerts the anti-tumor effect by inhibiting proliferation and metastasis of tumor cells, inducing apoptosis and autophagy of the cells, suppressing tumor angiogenesis, and regulating the immunity. In addition, it can enhance efficacy, reduce toxicity, and boost the sensitivity in the radiotherapy and chemotherapy. In this paper, articles were retrieved from China National Knowledge Infrastructure (CNKI), Web of Science, Pubmed, and Google Scholar with keywords such as "Phellinus, chemical components, and anti-tumor", and then the chemical components of Phellinus and the anti-tumor mechanisms were summarized. The findings are expected to lays a basis for further development and clinical application of this medicinal.

14.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 257-265, 2023.
Article in Chinese | WPRIM | ID: wpr-964967

ABSTRACT

As a rare Chinese medicinal material, Paridis Rhizoma is mainly distributed in Yunnan, Guangxi, and Guizhou in southwestern China, with the effect of clearing heat and detoxifying, alleviating edema and relieving pain, cooling liver and tranquilizing mind. It is particularly effective for injuries from falls, fractures, contusions and strains, snake bites, cold wind-induced convulsion, and other diseases, which has been used for more than 2 000 years. According to modern research, polyphyllin Ⅱ, one of the main active components of Paridis Rhizoma, belongs to diosgenin in structure. It has the anti-tumor, anti-inflammatory, antiviral, antibacterial, immune-regulating, antioxidant, and multidrug resistance-reversing activities, showing good application prospect. Especially, the anti-tumor effect of polyphyllin Ⅱ has attracted wide attention, and the mechanism is inhibiting proliferation, migration, and invasion of tumor cells, inducing cell cycle arrest, apoptosis, and autophagy, suppressing angiogenesis, and modulating tumor microenvironment. However, the pharmacokinetic results show that polyphyllin Ⅱ has low bioavailability in vivo due to the low solubility, poor absorption, unsatisfactory distribution, and slow metabolism, which limit the clinical application. In recent years, there has been an explosion of research on the adverse reactions of polyphyllin Ⅱ, such as the strong hemolytic activity and obvious cytotoxicity to liver, kidney, myocardium and cardiovascular cells. Thus, papers were retrieved from "CNKI", "VIP", "Wanfang Data", "PubMed", "Web of Science", and "Elsevier SD" with "Paris saponin Ⅱ", "Polyphyllin Ⅱ" as the main keywords, and the pharmacological activities and mechanisms, pharmacokinetics, and adverse reactions were summarized. The findings are expected to serve as a reference for the in-depth research, development, and utilization of polyphyllin Ⅱ.

15.
China Pharmacy ; (12): 631-635, 2023.
Article in Chinese | WPRIM | ID: wpr-964778

ABSTRACT

Bilirubin has good anti-inflammatory, antioxidant and immunomodulatory effects, but its poor water solubility and low bioavailability greatly limit its clinical application. Researchers have developed bilirubin into various nanoparticles, which effectively eliminate the limitation of low solubility of bilirubin with the advantage of dosage form, so that they can maximize its pharmacological activities such as anti-inflammatory, anti-oxidation and immune regulation. Bilirubin nanoparticles have great application potential in a variety of gastrointestinal diseases, liver and kidney diseases, skin diseases, autoimmune diseases, islet transplantation and targeted therapy of tumors (both as a direct anti-tumor drug and as a drug delivery system). The study of bilirubin nanoparticles will promote the clinical application of bilirubin and the development of related new drugs.

16.
China Pharmacy ; (12): 2034-2038, 2023.
Article in Chinese | WPRIM | ID: wpr-980602

ABSTRACT

Sanggenon C is a kind of flavonoid compound mainly extracted from the traditional Chinese medicine Morus alba. The pharmacological effects and mechanisms of sanggenon C are systematically reviewed and summarized, and it is found that this component can improve pulmonary fibrosis by regulating transforming growth factor-β1 and nuclear factor-κB; it can exert anti- tumor effects by inhibiting the proliferation of tumor cells and inducing the apoptosis of tumor cells; it can exert cardioprotective, neuroprotective and hepatoprotective effects by regulating multiple signaling pathways, such as calcineurin/nuclear factor of activated T cells 2, peroxisome proliferators-activated receptor α, and Ras homolog gene family member A/Rho-associated coiled- coil containing protein kinase, enhancing autophagy, reducing inflammatory response and reducing the level of oxidative stress; it can treat osteoporosis by inhibiting osteoclast uptake and promoting osteoblast formation; it has certain inhibitory effect on many enzymes; it can exert anti-inflammatory effects by regulating nuclear factor-κB signaling pathway; it can exert antioxidant effects by scavenging free radicals. However, researches on the pharmacological effects of sanggenon C mostly focus on the cellular and animal field, and the specific mechanism of action is not yet clear. In the future, basic research and clinical trials are still needed to explore and verify.

17.
Acta Pharmaceutica Sinica ; (12): 954-962, 2023.
Article in Chinese | WPRIM | ID: wpr-978774

ABSTRACT

With the development of small-molecule immunotherapy drugs, its combination with the programmed cell death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) antibodies would provide a new opportunity for cancer treatment. Therefore, targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity and considered as the next generation of tumor immunotherapy. In the present study, we investigated the anti-tumor role of salvianolic acid B (SAB) by regulating the PD-L1 level in tumors. Changes of total PD-L1 and membrane PD-L1 levels were determined by Western blot, flow cytometry and PD-1/PD-L1 interaction assays. The expression of mRNA level of PD-L1 was detected by real-time PCR. The cytotoxicity of activated peripheral blood mononuclear cell (PBMC) cells toward co-cultured tumor cells was measured by cell impedance assay and crystal violet experiment. Surface plasma resonance technique was used to analyze the direct interaction between SAB and ubiquitin carboxyl-terminal hydrolase 2 (USP2). The antitumor effect of SAB in vivo was examined by C57BL/6 mice bearing MC38 xenograft tumor (all animal experiments were conducted in accordance with the Animal Ethics Committee of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences). Western blot and flow cytometry assay showed that SAB can significantly downregulate the abundance of PD-L1 in RKO and PC3 cells in dose- and time-dependent manner. PD-1/PD-L1 binding assay revealed that SAB reduces the binding of tumor cells to recombinant PD-1 protein. Mechanism studies revealed that SAB can bind directly to USP2 protein and inhibit its activity, thus promote the ubiquitin-proteasome pathway degradation of PD-L1 proteins. In addition, Cell impedance and crystal violet staining indicated that SAB enhances the killing activity of co-cultured PBMC cells toward tumor cells. MC38 tumor transplanted mouse experiments revealed that SAB treatment displayed significant suppression in the growth of MC38 tumor xenografts in C57BL/6 mice with an inhibition rate of 63.2% at 20 mg·kg-1. Our results demonstrate that SAB exerts its anti-tumor activity by direct binding and inhibiting the activity of USP2 and reducing the PD-L1 level. Our study provides an important material basis and scientific basis for the potential application of SAB in tumor immunotherapy drug targeting USP2-PD-L1 axis.

18.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 226-238, 2023.
Article in Chinese | WPRIM | ID: wpr-975176

ABSTRACT

Pyroptosis, an atypical new cell death mode other than apoptosis and necrosis, has been discovered in recent years. Pyroptosis depends on the cleavage of gasdermins (GSDMs) by Caspases. The activated GSDMs act on the plasma membrane to form a perforation, which results in cell lysis and triggers inflammation and immune response. Pyroptosis can be induced by four distinct signaling pathways, including canonical and non-canonical inflammasome pathways, apoptosis-associated Caspases-mediated pathway, and granzyme pathway. In these signaling pathways, GSDMs are the executors of pyroptosis. Pyroptosis is associated with the death of tumor cells and the inflammatory damage of normal tissues. Recent studies have demonstrated that moderate pyroptosis can lead to tumor cell death to exert an anti-tumor effect, and meanwhile stimulate the tumor immune microenvironment, while it can promote tumor development. Despite the good performance, drug-based anti-tumor therapies such as tumor immunotherapy, chemotherapy, and targeted therapy have some shortcomings such as drug resistance, recurrence, and damage to normal tissues. The latest research shows that a variety of natural compounds have anti-tumor effects in the auxiliary treatment of tumors by mediating the pyroptosis pathways in a multi-target and multi-pathway manner, which provide new ideas for the study of anti-tumor therapy. We reviewed the molecular mechanism of pyroptosis and the regulatory role of pyroptosis in tumors and tumor immune microenvironment, and summarized the recent research progress in the natural medicinal components regulating pyroptosis in anti-tumor therapy, with a view to providing ideas for the research on the anti-tumor therapy based on pyroptosis.

19.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 264-272, 2023.
Article in Chinese | WPRIM | ID: wpr-973769

ABSTRACT

Malignant tumors, with the increasing crude morbidity and mortality year by year, have become the major diseases threatening human health. The conventional therapeutic drugs against tumors have serious adverse reactions, which can cause a heavy burden on patients. The active components of Chinese medicine can effectively inhibit tumor growth, improve the quality of life of patients, and have few toxic and side effects. Alkaloids of Chinese medicine are natural organic compounds widely existing in a variety of Chinese herbal medicines. In recent years, they have attracted more and more attention because of their anti-tumor effect. The anti-tumor mechanisms of alkaloids of Chinese medicine mainly include the induction of apoptosis, inhibition of tumor cell migration and invasion, suppression of proliferation, induction of autophagy of tumor cells, cell cycle arrest, inhibition of tumor angiogenesis, regulation of microRNA, and modulation of immunity. In addition, Chinese medicine alkaloids can also reverse tumor drug resistance and reduce the stemness of tumor stem cells. Alkaloids of Chinese medicine can regulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), mammalian target of rapamycin (mTOR), Notch, Hedgehog, Wnt/β-catenin, and other signaling pathways to participate in the processes of tumor proliferation, invasion and metastasis, autophagy and apoptosis, and affect the occurrence and development of tumors in multiple links and ways. The derivatives and nano-preparations of alkaloids can improve the solubility, utilization, and anti-tumor activity of alkaloids, bringing a broader prospect for the clinical application of alkaloids. This review summarized the recent anti-tumor research on alkaloids, their representative derivatives, and nano-preparations to provide references for the in-depth research on the anti-tumor effect of alkaloids.

20.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 274-282, 2023.
Article in Chinese | WPRIM | ID: wpr-973158

ABSTRACT

Malignant tumors seriously threaten human life and health. Radiotherapy and chemotherapy are the conventional methods for the clinical treatment of advanced tumors. The prognosis and efficacy are still far from satisfactory due to the radiotherapy has serious adverse effects on the body and the chemotherapy often causes problems such as tumor resistance and cell proliferationinhibition. Therefore, the search for new, safe, and effective anti-tumor drugs and the elucidation of their molecular mechanisms are effective measures for clinical treatment of tumors and improvement of patients' quality of life. Active ingredients derived from Chinese herbal medicines and natural products have gradually become a hot spot in the research and development of anti-tumor drugs due to their multi-target and multi-channel anti-tumor pharmacological activity characteristics and their advantages such as less adverse reaction on the body. Bruceine D is a class of tetracyclic triterpenoids extracted from the fruit of the Chinese herbal medicine Bruceae Fructus, with anti-inflammatory, anti-malarial, anti-parasitic, and other pharmacological activities, and its anti-tumor activity is particularly significant. Pharmacological studies have found that bruceine D can regulate various cellular physiological activities such as proliferation, apoptosis, invasion, and migration of lung cancer, liver cancer, pancreatic cancer, intestinal cancer, and other cancer cells by targeting different signaling pathways. Bruceine D can be used in combination with other chemotherapeutic drugs to improve the sensitivity of tumor cells to chemotherapeutic drugs, thereby reducing the adverse effect of chemotherapy. Clinical application practice has shown that Bruceae Fructus oil emulsion injection containing bruceine D has significant advantages in the efficacy and safety of tumor treatment. Although there are many studies on the antitumor pharmacological activity of bruceine D and its clinical efficacy is significant, the specific antitumor molecular mechanism of bruceine D is still unclear, and there is a lack of systematic review on the existing antitumor mechanism of bruceine D. Therefore, based on the research on bruceine D in China and abroad in recent years, this paper reviewed the anti-tumor effect and related molecular mechanisms of bruceine D from six aspects, namely, tumor cell proliferation, apoptosis, metastasis and invasion, glucose metabolism process, autophagy, and chemotherapy sensitivity. This paper is expected to provide a pharmacological basis and scientific reference for the antitumor drug development and clinical application of bruceine D.

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