ABSTRACT
Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.
Subject(s)
Humans , Female , Medicine, Chinese Traditional , Vascular Endothelial Growth Factor A/metabolism , Endothelial Cells/metabolism , Angiogenesis , Angiogenesis Inhibitors/therapeutic use , Ovarian Neoplasms/genetics , Neovascularization, Pathologic/geneticsABSTRACT
Because the early symptoms of ovarian cancer are not typical and there is a lack of effective screening methods， most patients are diagnosed at an advanced stage， which seriously endangers the health of modern women. Platinum-based chemotherapy after tumor reduction is the first choice for patients with advanced and recurrent ovarian cancer， but almost all patients with recurrent ovarian cancer will eventually develop platinum resistance. Therefore， the search for natural， safe， and effective chemotherapeutic sensitizers has become an urgent and important topic in the study of ovarian cancer. With the increasingly extensive application of traditional Chinese medicine （TCM） in the treatment of cancer， the research on Chinese herbal monomers is also deepening， and the mechanisms of Chinese herbal monomers in intervening in cisplatin （DDP）-induced resistance of ovarian cancer is becoming increasingly clearer. Based on the research status of Chinese herbal monomers available in many Chinese and English databases， it was found that Chinese herbal monomers were involved in the reversal of DDP-induced resistance of ovarian cancer via many routes， mainly through increasing the intracellular drug concentration， reversing the blocked apoptosis， correcting the abnormal intracellular signaling pathway， enhancing DNA damage and inhibiting DNA repair， regulating intracellular autophagy， and suppressing epithelial mesenchymal transition （EMT）. Chinese herbal monomers weaken the resistance of ovarian cancer to DDP from multiple targets and enhance the toxicity of DDP to ovarian cancer cells in vitro and transplanted tumors in vivo. Therefore， Chinese herbal monomers are expected to become natural sensitizers for ovarian cancer chemotherapy with DDP. However， the current studies on Chinese herbal monomers are still confined to the single experimental type， and their action mechanisms and toxic and side effects remain to be further clarified. The application of Chinese herbal monomers for sensitizing DDP chemotherapy still needs to be verified by multi-target， multi-level experimental studies and large-scale clinical studies in the future.
ABSTRACT
Ovarian cancer （OC） is one of the three major gynecological malignancies. Due to its insidious onset at the early stage，most of OC patients are diagnosed at the advanced stage， making it become one of the most deadly gynecological tumors and thus a hot topic in the field of gynecology and oncology. Guizhi Fulingwan is a classic Chinese herbal compound derived from Synopsis of Golden Chamber （《金匮要略》） for the treatment of abdominal mass in women on account of its efficacy in resolving stasis， generating new blood， and eliminating mass. The articles concerning the treatment of OC with Guizhi Fulingwan were searched from such databases as China National Knowledge Infrastructure （CNKI）， PubMed，Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP） and collated for expounding its action mechanisms， in order to provide ideas for further research on its pharmacological effects，clinical application， and promotion. Clinically，Guizhi Fulingwan has been proved to control the growth of myoma，correct serological indexes，enhance chemotherapy sensitivity and anti-tumor immunity，reduce postoperative recurrence rate， and improve the quality of life of patients. As revealed by experimental research，Guizhi Fulingwan alleviates the pathological state of animal and cell models by promoting mitochondrial apoptosis and tumor immunity，inhibiting vascular factors，inducing cell cycle arrest， and reversing multidrug resistance. Guizhi Fulingwan exerts a certain therapeutic effect on OC through multi-target and multi-channel mechanisms， reflecting the advantages of traditional Chinese medicine in treating OC.
ABSTRACT
Ovarian cancer， one of gynecological malignancies， is often diagnosed at the late stage because of the atypical early symptoms and has become a major killer of women. Research has found that the co-evolution of tumor cells and their surrounding microenvironment is an important cause for the occurrence and development of ovarian cancer. It is believed in traditional Chinese medicine （TCM） that Yin and Yang are the roots of everything， and their balance， namely Yin being at peace and Yang being compact （“Yin Ping Yang Mi”） is a sign of good health. The mutual opposition， restriction， and rooting of Yin and Yang as well as their waning and waxing and transformation are the keys to maintaining the balance. In TCM， ovarian cancer falls into the category of abdominal mass， which results from the struggle between healthy Qi and evil Qi. When the healthy Qi is deficient and the evil Qi is excessive， the balance between Yin and Yang will be destroyed， triggering the body and ovarian cancer microenvironment as well as the relevant factors in the inflammatory microenvironment to be mutually opposed， restricted， and transformed， highly consistent with the dynamic development of Yin and Yang. At present， the studies concerning TCM intervention in the inflammatory microenvironment of ovarian cancer mostly focus on the signaling pathways to reveal the advantages of TCM multiple components against cancer cells via multiple targets， but they fail to explain the TCM efficacy from the perspective of Yin-Yang balance. Therefore， guided by the concept of Yin-Yang balance， this paper macroscopically and microscopically explored the effects of the changed factors in inflammatory microenvironment on the occurrence and development of ovarian cancer， and put forward that the prevention and control principles of ovarian cancer should lie in the "adjustment of Yin-Yang balance"， accompanied by healthy Qi reinforcement and pathogen elimination. This paper has laid the foundation for the elucidation of modern research achievements regarding the ovarian cancer microenvironment with TCM theory and provide a theoretical basis for the clinical treatment of ovarian cancer with integrated TCM and western medicine.
ABSTRACT
Ovarian cancer is a kind of malignant tumor in female reproductive system with a high incidence. This disease is insidious at its early stage and the symptoms are not typical. Most of the patients have reached advanced stage by the time of diagnosis， seriously threating women's life and health. Many signaling pathways are involved in the formation and development of ovarian cancer， among which the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway is one of the key regulatory pathways. In recent years， traditional Chinese medicine （TCM） has obtained wide attention in treatment of tumors due to its advantages of high safety and less adverse reactions， and more and more attention has been paid to the study of TCM monomers. Molecular biology studies have shown that TCM monomers can play a role against tumor by regulating multiple targets. By reviewing the literature and searching several databases， we found that TCM monomer can play an important role in the growth， proliferation， invasion and migration， apoptosis， autophagy and reversal of drug resistance of ovarian cancer cells by regulating PI3K/Akt signaling pathway. According to the existing studies， TCM monomers have a certain effect on ovarian cancer， but there are still many problems. Although the mechanisms of some TCM monomers have been clarified in the treatment of ovarian cancer， such TCM monomers are only limited to the tumor-bearing nude mice in vivo and experimental studies on in vitro cells， and further studies are needed in the future. In addition， in the future researches， ovarian cancer syndrome differentiation and targeted therapy can be linked to the TCM flavors， efficacy and indications to further develop the advantages of TCM. Based on the current research situation at home and abroad， this paper summarized the research progress of targeted intervention of TCM monomers in ovarian cancer by regulating PI3K/Akt signaling pathway， in order to provide reference for further research of TCM monomers， and provide important ideas for the development of targeted treatment of ovarian cancer with TCM.
ABSTRACT
Objective: With Bletillae Rhizoma gelatin as the main film-forming materials, Erhuangsan was developed into a sustained-release double-layer membrane for vagina. Method: Taking hydroxypropyl methyl cellulose(HPMC) and Bletillae Rhizoma gelatin as the film-forming materials of Coptidis Rhizoma-Alumen membrane layer, sodium carboxymethyl cellulose(CMC-Na) and Bletillae Rhizoma gelatin as the film-forming materials of Catechu membrane layer, glycerol as plasticizer, Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane was prepared.Central composite design-response surface methodology was used to optimize formulation of this preparation with appearance quality score, adhesion force and in vitro cumulative release as indexes. Result: Optimum formulation of Catechu membrane layer was 1.61% of CMC-Na, 3.81% of Bletillae Rhizoma gelatin and 8.49% of glycerol;optimum formulation of Coptidis Rhizoma-Alumen membrane layer was 1.15% of HPMC, 3.41% of Bletillae Rhizoma gelatin and 10.02% of glycerol. Conclusion: The optimized formulation is stable and feasible.Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane has characteristics of advanced dosage form and convenient use, providing a feasible modern Chinese medicine preparation for treatment of cervical cancer, and accumulating data for the research of Chinese medicine film agent.
ABSTRACT
Because it can not only directly reach the lesion site to play a local therapeutic effect, but also avoid the liver first pass effect and play a systemic therapeutic effect, vaginal mucosal administration has attracted more and more attention from domestic and foreign scholars in the treatment of vaginitis, cervicitis and other diseases. This article introduces the physiological characteristics of the vagina and discusses the factors affecting drug absorption. The vaginal mucosal drug-administered preparations, which are contained in the drug database of U.S. Food and Drug Administration(FDA) and China Food and Drug Administration(CFDA), and listed in the 2015 edition of Chinese Pharmacopoeia, are taken as the research objects. And the application of their dosage forms, indications and other aspects were sorted out and analyzed. The related literature on vaginal mucosal drug delivery systems in recent years was reviewed, and the dosages forms and in vitro and in vivo evaluation were summarized. Some problems in the study of vaginal mucosal drug preparations have been pointed out:①the western medicine preparations are widely used, and the related Chinese medicine preparations have been developed less; ②the majority of dosage forms are tablets, suppositories and other conventional dosage forms; ③there are few studies on the evaluation of vaginal mucosal preparations in vitro and in vivo. It is suggested that the future development of vaginal mucosal drug delivery system can be a useful attempt in the application of new technologies and methods, such as combination of drugs, high adhesion excipients, liposomes, etc;so as to provide reference for the application and improvement of vaginal mucosal drug delivery system.
ABSTRACT
Due to the definite curative effect,stable drug properties and low incidence of adverse reactions,the external traditional Chinese medicine(TCM) ointment for rheumatism treatment has attracted more and more attention from scholars at home and abroad.Based on the external TCM ointment for the treatment of rheumatism approved by China Food and Drug Administration(CFDA),this paper would comb and analyze their dosage forms,varieties,specifications,etc.On the other hand,this article summarizes the application of the new formulation technology,prescription research,study on the forming process,pharmacodynamics and safety research,etc.The problems existing in this area were pointed out,such as lack of new preparations;less research on the penetration material basis,the penetration enhancing mechanism,and the penetration enhancing law;the selection of detection indicators of quality control standards is not comprehensive enough;qualitative and quantitative studies of pharmacokinetics are relatively scarce and so on.Meanwhile,proper measures and suggestions are put forward.Not only the formulation classification and specification description of external TCM ointment should be standardized,but also new dosage forms such as intelligentized,controlled release and targeted preparations of Chinese medicine should be actively introduced;the study of transdermal activity of transdermal enhancer itself should be strengthened,and investigating the correlation between the transdermal absorption of the agent itself and promoting transdermal absorption;the biological effect index or indicators that combine chemical and biological effects should be used,and learning from the latest research achievements of multidimensional spectroscopy of Chinese herbal medicine,thereby establishing scientific detection indicators and quality control methods that conform to modern transdermal concept.
ABSTRACT
<p><b>OBJECTIVE</b>To study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice.</p><p><b>METHODS</b>Growth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot.</p><p><b>RESULTS</b>The inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05).</p><p><b>CONCLUSIONS</b>Intraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.</p>