Function And Mechanism Of Anti-tumor Of A Synthetic Compound QW78

Malignant tumor is a major threat to public health with increasing incidence and mortality and is leading cause of death worldwide.Chemotherapy consists in the major first-line therapeutics against malignant tumor.With the development of chemotherapeutic drugs and regimens,it brings much benefit to patients.But many different chemotherapeutic drugs lead to tumor drug resistance and serious cytotoxicity which often limits its clinical use.Adriamycin and Taxol as clinical first-line anti-tumor drugs,their use is often accompanied by drug resistance and cytotoxicity.Based on the clinical problems,we screened a novel synthetic candidate compound QW78 by optimized phenotypic screening.It exerted potent anti-growth on many malignant tumor cells including colon cancer,liver cancer and osteosarcoma,similar result in Adriamycin and Taxol-resistant tumor cells at very low concentration.On the other hand,it had less cytotoxicity on normal cells which showed weaker anti-proliferation compared to tumor cells.From the exploration of molecular mechanism,our data showed QW78 resulted in DNA double-strand breaks(DSBs)which is considered to be the most serious of all DNA damage,furthermore induced cell cycle arrest at G2/M and cell apoptosis under unfinished DNA repair.In animal study,we found QW78 suppressed tumor growth on classical tumor and drug-resistant tumor xenograft models at nontoxic doses.More importantly,it had higher safety than clinical chemotherapy drugs,such as Adriamycin and Taxol.In conclusion,our study found a novel synthetic compound QW78 which showed potent anti-proliferation activity on tumor cells including drug-resitant tumor cells in vitro and in vivo.It implied QW78 maybe a potential candidate which had less cytotoxicity.