Gemcitabine-Resistance Reversion of Cucurmosin in Human Pancreatic Cancer Cells

Abstract

Objective To investigate the effects of cucurmosin (CUS) on proliferation and drugs resistance in gemcitabine (GEM) human pancreatic cancer cell PANC-1RG7. Methods The ultrastructural changes of PANC-1RG7 cells after CUS intervention were observed by transmission electron microscope. Flow Cytometer (FCM) was used to detect the effect of CUS on the growth cycle of PANC-1RG7 cells. We used colony formation experiment, Sulforhodamine B assays and subcutaneous implantation tumor model to observe the proliferation inhibition and reversal drug-resistance reversion of CUS on PANC-1RG7 in vitro and in vivo. Western blot was used to observe the expressions of RRM1, RRM2, PI3K, Akt, mTOR and other proteins related to apoptosis after CUS intervention. Results After CUS intervention, PANC-1RG7 cells were obviously apoptotic with large number of vacuoles and apoptotic bodies. Compared with parental cell PANC-1, GEM-resistant cell PANC-1 was more sensitive to CUS. The combination of GEM and CUS at different concentrations showed synergistic effect. At the concentration of CUS with the inhibition rate of 10%, the reversal multiples and the reversal efficiency were 1.78±0.65 and 50.13±16.87%, respectively. Subcutaneous implantation tumor model confirmed the proliferation inhibitory effect of CUS in vitro. Western blot confirmed that CUS down-regulated the expressions of RRM1, RRM2, PI3K, Akt and mTOR. Conclusion CUS can significantly inhibit PANC-1RG7 cell proliferation in vivo and in vitro, and can reverse cell GEM-resistance.