Study On The Anti-lung Cancer Mechanism Of The Combination Of Rhizoma Paridis Saponins And Curcumin

Rhizoma Paridis saponins(RPS)and Curcumin(CUR)have broad-spectrum antitumor activity,which are natural compound.CUR has the low bioavailability,so its anti-cancer effects are suppressed.The anticancer efficiency of CUR could be improved by the change of curcumin formulations or combined with other drugs.In our study,CUR was made into the curcumin-β-cyclodextrin(CD15)by the saturated aqueous solution method.CD 15 was characterized by Fourier transform infrared(FTIR)and UV spectra analyses.An optimized CD15 was evaluated for intracellular uptake and anti-cancer activity.As a result,cellular uptake assays and animal experiment demonstrated that CD 15 enhanced curcumin delivery and improved its therapeutic efficacy compared with free curcumin in vivo and in vitro.Therefore,through the regulation of MAPK/NF-κB pathway,CD 15 up-regulated p53/p21 pathway,down-regulated CyclinE-CDK2 combination and increased Bax/caspase 3 expression to induced cellar apoptosis and G1-phase arrest.In conclusions,these results suggested that CD 15 formulation could improve curcumin delivery,and the study of anti-ancer mechanism provide prospective strategies for cancer therapy.Rhizoma Paridis saponins II(RPSII)has anticancer activity,and the study shown that it induced autophagy and apoptosis in dose-and time-dependent manners,and induced autophagy associated with apoptosis.Blockade of autophagy with CQ attenuated apoptosis,which indicated RPSII induced apoptosis by activaty of autophagy.RPSII can reduce intracellular ROS,while regulation of reactive oxygen species(ROS)by N-acetyl cysteine(NAC),gallic acid(GA)and H2O2 could not influence autophagy.So,RPSII induced ROS-independent autophagy and autophagy-dependent apoptosis.RPSII activated JNK and inhibited PI3K,AKT and mTOR,and CQ could reduce p-JNK and p-PI3K.PSII induced apoptosis via activation of autophagy,which might be associated with the activation of JNK and inhibition of PI3K/AKT/mTOR pathway.All in all,our research increased the understanding of the role of PSII regulating autophagy and apoptosis,which would hopefully provide prospective strategies for cancer therapy.In order to improve the anti-cancer effects,CUR and RPS combinated to treat lung cancer cells.RPSII as one of the main effective compounds in four RPS was combined with CUR.As a result,the combination of(0.125μM-2μM)RPSII and(15μM)CUR displayed a synergistic anticancer effect through promoting the cellular uptake of CUR on different lung cancer cells.The combination of PSII and CUR displayed synergistic anticancer effect through inhibiting proliferation,blocking cell migration,reducing ROS,and inducing apoptosis and autophagy.Western blot suggested that the combination of RPSII and CUR induced apoptosis via MAPK/PI3K/Akt pathway.Meanwhile,the combination affectd the expression of p-JNK,p-p38 and p-Erkl/2,suppressed PI3K,p-AKT and NF-κB.Therefore,PSII combined with CUR had a synergistic anti cancer effect on lung cancer cells.These findings provided a rationale for exploring the potential benefits of the combination of curcumin with RPSII for treatment of lung cancer in future.