Mechanism of Chinese Herbal Monomers Against Cisplatin-induced Resistance of Ovarian Cancer： A Review / 中国实验方剂学杂志

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.

Mechanisms of Guizhi Fulingwan Against Ovarian Cancer： A Review / 中国实验方剂学杂志

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.

Effect of Curdione on MDA-MB-231 Cell Cycle and Apoptosis / 中国实验方剂学杂志

Objective:To investigate the effects of curdione on the proliferation， apoptosis and cell cycle of triple negative breast cancer cell line MDA-MB-231. Method:MDA-MB-231 cells were cultured<italic> in vitro</italic> with capecitabine （positive control） and curdione at different concentrations （125， 250， 500， 1 000， and 2 000 μmol·L^-1）， respectively， for detecting their viability using the cell counting kit-8 （CCK-8） at 24 and 48 h. Three effective inhibitory concentrations （250， 500， and 1 000 μmol·L^-1） against cell proliferation were selected for subsequent experiments. The effect of curdione on cell cycle was determined by flow cytometry combined with propidium iodide （PI） staining. After the set-up of high-concentration （2 000 μmol·L^-1） group， the effect of curdione on cell mitochondrial membrane potential was measured by JC-1（5，5，6，6-tetrachloro-1，1，3，3-tetraethylbenzimidazolylcarbocyanine iodide） staining， followed by the detection of cell apoptosis by flow cytometry combined with Annexin V-FITC/PI double staining. The changes in cell cycle status and apoptosis-related protein expression following curdione intervention were assayed by Western blot. Result:Compared with the blank control， curdione at 250， 500， 1 000， and 2 000 μmol·L^-1significantly inhibited the proliferation of MDA-MB-231 cells （<italic>P</italic><0.01）， exhibiting a concentration- and time-response relationship. The half maximal inhibitory concentration （IC₅₀） values at 24 and 48 h were 1 607 and 1 401 μmol·L^-1， respectively. Curdione at 250， 500， and 1 000 μmol·L^-1 arrested cells in G₁ phase. Curdione at 250 μmol·L^-1had no effect on cell mitochondrial membrane potential， which， however， declined significantly in the 500， 1 000， and 2 000 μmol·L^-1groups （<italic>P</italic><0.05， <italic>P</italic><0.01）. Curdione at 250， 500， and 1 000 μmol·L^-1obviously increased the proportion of apoptotic cells （<italic>P</italic><0.05， <italic>P</italic><0.01）. Curdione at each concentration elevated the Bcl-2-associated X protein （Bax）/B-cell lymphoma 2 （Bcl-2） ratio （<italic>P</italic><0.05， <italic>P</italic><0.01）， but did not change the cysteinyl aspartate-specific protease-3 （Caspase-3） expression. The protein expression levels of Caspase-9， cleaved Caspase-9， cleaved Caspase-3， p53， and p21 were up-regulated （<italic>P</italic><0.05）. Conclusion:A certain concentration of curdione inhibits the proliferation of MDA-MB-231 cells， which may be related to its efficacy in arresting cell cycle and inducing apoptosis.

Study Progress of Effect of Traditional Chinese Medicine Monomer in Intervening Ovarian Cancer by Regulating PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

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.