Mechanism of Cancer Drug Resistance and Reversal Effect of Chinese Medicine： A Review / 中国实验方剂学杂志

Malignant tumor is a serious threat to human life and health. The prevalence and mortality of malignancies in China are increasing year by year. Conquering cancer has become a difficult problem for human beings. Chemical drug therapy combined with molecular targeted therapy is a general and preferred anti-tumor clinical scheme， but the side effects and the drug resistance of cancer cells often hinder the efficacy. Therefore， it is of great significance to study the mechanism of drug resistance and the methods to reverse drug resistance. Chinese medicine has the characteristics of complex components， multiple targets， low toxicity， etc. A large number of experimental studies have demonstrated that the effective components or extracts of Chinese medicine can inhibit the proliferation， migration， and invasion of cancer cells， and induce apoptosis， autophagy， differentiation， and senescence. In clinical practice， Chinese medicine has been applied to the protection against ttumor， adjuvant treatment， and later consolidation. The research on Chinese medicine is expected to promote drug resistance reversal and cancer therapy. Studies have shown that the combination of Chinese medicine and chemotherapy can reverse drug resistance and increase efficacy， which has become the mainstream trend of cancer treatment. This study reviewed the mechanisms of the drug resistance of cancer cells induced by self-protective autophagy， gene mutation， high expression of enzymes， abnormal signaling pathways， and abnormal expression of RNA and protein， and summarized how compounds isolated from Chinese medicine， single drug and its extract， and classic anti-cancer prescription reversed the drug resistance to lay a solid foundation for the further investigation of the anti-tumor effect of Chinese medicine.

Effect of Notoginseng Total Saponins on Changing Multidrug Resistance in HepG2/ Adriamycin Cells Through ERK/Akt Signaling / 中国实验方剂学杂志

Objective:To investigate the effect of notoginseng total saponins （TNS） on adriamycin （Adr） resistance in HepG2/Adr cells and the expression and activity of the mechanisms as the modulators of multi-drug resistance， so as to explore the possible mechanism of extracellular signal-regulated kinase （ERK） and protein kinase B （Akt） signaling pathways in reversing the resistance of HepG2/Adr cells mechanism. Method:Effect of TNS on HepG2/Adr cell proliferation was detected by thiazole blue （MTT） method. HepG2/Adr cells were treated with different concentrations （100， 50， 25， 0 mg·L^-1） of TNS and （20 μmol·L^-1） Adr respectively， and a blank group was set. The high-content screening platform was used to detect the accumulation of Adr in HepG2/Adr cells after 40 minutes， 3 hours and 6 hours. Western blot was used to detect the expression of P-glycoprotein /multidrug resistance/ATP binding cassette subfamily B member 1（P-gp/MDR1/ABCB1） and other drug resistance-related proteins and the main protein expression of ERK/Akt signaling pathway. The change of MDR1 on cell membranes was observed by laser confocal microscopy. Result:Compared with HepG2 cells， the expression of MDR1 in HepG2/Adr cells was significantly increased （<italic>P</italic><0.01）. Compared with the Adr group， the half-inhibitory concentration （IC₅₀） of TNS （25， 50， 100 mg·L^-1） and Adr （20 μmol·L^-1） co-administration group on HepG2/Adr cells <italic>in vitro</italic> significantly reduced （<italic>P</italic><0.01）， and the highest reversal multiple was 10 times. Compared with the Adr group， the co-administration group could significantly increase the accumulation of Adr in the cells （<italic>P</italic><0.05） in a dose-dependent manner. Compared with the blank group， the co-administration group could significantly reduce MDR1， ABC semitransporter （ABCG2）， multidrug resistance associated protein （MRP1）， ERK， phosphorylated extracellular regulatory protein kinase （p-ERK）， Akt， phosphorylated protein kinase B （p-Akt）， mammals， rapamycin target protein （mTOR） and phosphorylated mammalian rapamycin target protein （p-mTOR） （<italic>P</italic><0.05）， with the same results in the doxorubicin group. Compared with the blank group， there was no significant difference in the distribution and fluorescence intensity of MDR1 on the cell membrane between the Adr group and the notoginseng total saponins （25 mg·L^-1） group. Compared with the blank group and the doxorubicin group， TNS could significantly reduce the distribution of MDR1 on the cell membrane （<italic>P</italic><0.05）. Conclusion:TNS can inhibit the ERK/Akt pathway， reduce the expression of MDR1， and significantly increase the accumulation of doxorubicin in HepG2/Adr cells， which may be one of the mechanisms of notoginseng total saponins in reversing resistance.

Inhibitory effect of PI3Kδ inhibitor idelalisib on proliferation of human myeloid leukemia cells and the reversal effect on drug resistance to adriamycin / 中南大学学报(医学版)

OBJECTIVES@#To investigate the effect of adriamycin (ADM), idelalisib or ADM and their combination on cell proliferation and intracellular concentration of ADM, and to explore the reversal effect of idelalisib on drug resistance to ADM.@*METHODS@#The K562 and K562/ADM cells were respectively treated with ADM and idelalisib at different concentrations. The 50% inhibitory concentration (IC@*RESULTS@#The cell survival rates were significantly decreased in a dose-dependent manner when the cells were treated with different doses of ADM (0.001-10.000 mg/L ). The IC@*CONCLUSIONS@#Idelalisib exerts effect on inhibition of the proliferation in myeloid leukemia K562 and K562/ADM cells, which may partially reverse the drug resistance of K562/ADM cells to ADM. The mechanisms for the effect of idelalisib may be related to increasing the accumulation of ADM and inducing the cell apoptosis in the K562 and K562/ADM cells.

Advanced progress on the effect and mechanism of tetrandrine / 国际中医中药杂志

Tetrandrine(TET), bis-benzylisoquinoline alkaloid, belonging to the traditional Chinese medicine, has attented great attention by researchers in the phamalogical and medical industries. It was found that tetrandrine had effect of anti-tumor, anti-microbial, reversal of multi-drug resistance, anti-inflammatory and anti-diabetic. This article reviewed the research on the biological activity through inhibition of protein expression and signal pathway regulation of tetrandrine, and summarized the problem and solution of tetrandrine in order to provide the basis for the further studies.