ABSTRACT
Adriamycin resistance in HCC seriously hinders the treatment of patients, it is necessary to investigate the mechanisms. Autophagy is involved in adriamycin resistance and JNK2 is related to autophagy. However, whether JNK2 inducing drug resistance though autophagy is unknown. GL-V9, a new synthesized flavonoid derivative, has been proved of its anti-tumor effects. The aim of the study is to explore the role of JNK2-related autophagy on adriamycin-induced drug resistance and the effects of GL-V9 on reversing adriamycin resistance. We concluded that JNK2 played an important role in drug resistance induced by adriamycin. The high expression of JNK2 activated protective autophagy in Hep G2-DOXR cells under non-stress condition, which protected cells from drug attacking. Furthermore, we found that GL-V9 reversed adriamycin resistance by blocking the JNK2-related protective autophagy in HCC.
ABSTRACT
@#To investigate the apoptotic effect of flavonoid compound GL-V9 on human gastric cancer cells and its potential mechanism, MGC-803 and BGC-823 cells were treated with GL-V9. MTT assay was performed to assess the growth inhibition effects on MGC-803 and BGC-823 cells under different concentrations of GL-V9. Annexin V-FITC/PI staining assay was employed to observe the apoptotic rate of GL-V9 cells with the treatment of GL-V9. DAPI staining was performed to observe the nuclear morphological changes using fluorescence microscopy. Activation of caspase-9 and caspase-3 was analyzed by Western blotting. Ca2+ concentration in gastric cancer cells was detected by Fluo-3 AM staining assay. Results showed that GL-V9 could inhibitcell viability, change the nuclear morphologyl, activate caspase-9 and caspase-3 and induce the apoptosis in gastric cancer cells. The mechanism of the induction of apoptosis in MGC-803 cells under the treatment of GL-V9 may aetivate the Ca2+ associated mitochondrial apoptosis pathway.