Evaluation And Investigation On Antitumor Activity And Anticancer Mechanism Of Quaternary Phosphonium Chitosan

Although the cancer is a serious disease threatening to human health,the current clinical treatments of cancer still have some limitation.Therefore,in order to avoid the defects and to treat cancer more effectively,the focus on new anticancer drugs and new therapeutic strategies has become more important.Triphenylphosphonium salts(TPP)and chitosan(CS)are promising candidates for biomedical application due to their special properties,such as biocompatibility,low cytotoxicity and antitumor activity.In this study,two different quaternary phosphonium chitosan N-TPP-CS and TPPB-CS were synthesized by ring-opening method and amide method.The water soluble TPPB-CS was chosen to evaluate its antitumor activity in vitro and in vivo as well as to investigate its anticancer mechanism through examing the cell cycle,ROS and ??m level,TNF-? and VEGF secretions.The major conclusions are as following:(1)As TPPB was grafted onto chitosan using chemical synthesis,TPPB-CS possessed an enhanced water solubility compared with chitosan and it was suitable to be used as material to investiagete its antitumor activity and antitumor mechanism.(2)TPPB-CS showed a selectivity-toxicity between cancer cell lines(MG-63 and HepG2 cells)and normal cells(NIH3T3 cells).Also a significant effect on inhibiting cell migration but not cell invasion in Hep G2 cells was observed in vitro.These results demonstrated that the antitumor activity of TPPB-CS in vitro was attributed to inhibiting the proliferation and migration in tumor cells.(3)The results of animal experiments in vivo showed that TPPB-CS could effectively inhibit tumor growth,performed no systemic acute toxity and little toxic side effects.(4)It was found that the antitumor activity of TPPB-CS may related to delay the cell cycle in S phase,alter the ROS and ??m level and regulate the secretion of TNF-? and VEGF.Therefore,due to the antitumor activity and biosafety of TPPB-CS,it can become a promising anticancer drug for clinical therapy.