The Proliferation, Inhibition And Mechanisms Of Paclitaxel Combined With Cisplatin In Human Breast Cancer Cell Line MCF-7

Objective：To investigate the inhibitory effects of paclitaxel alone or combined withcisplatin against human breast cancer line MCF-7in vitro, and to explore the relatedmechanisms with MAPK pathway and Bcl-2gene family.Methods：Human breast cancer line MCF-7was treated with paclitaxel with/withoutcisplatin alone and combined with ERK pathway inhibitor (U0126) and JNK pathwayinhibitor (sp600125). Proliferation and50%inhibitory concentration (IC50) werecalculated by using Cell Counting Kit-8assay. Flow cytometry was used to determinecell cycle distribution, and Western Blot was used to detect the protein expressionlevel changes of MAPK pathway members, Bcl-2and Bax when cells were givendifferent treatments.Results：Paclitaxel(0.025-0.4μM) combined with cisplatin (1-16μM)showed an obvioussynergistic effect（CI<0.95）. Sp600125could significantly inhibit MCF-7growth invitro.Sp600125combined with paclitaxel or cisplatin had a better antitumor activitythan paclitaxel or cisplatin used alone. The cells at G2/M decreased compared withpaclitaxel group while increased compared with cisplatin group in response topaclitaxel and cisplatin treatment. Combination of paclitaxel and cisplatin was foundto decrease P-ERK, Bcl-2protein levels in contrast with paclitaxel group or cisplatingroup and increase P-JNK/P-SAPK, P-p38, protein levels, while the ratio Bcl-2/Baxwere lower in contrast with control group after48hours. Conclusion:(1) Combination effects of paclitaxel and cisplatin in vitro showed synergisticeffect. JNK pathway inhibitor combination with paclitaxel and cisplatin showed morepowerful inhibition on MCF-7cells than the two drug combination.(2) Combination of paclitaxel and cisplatin seems to limit the accumulation ofMCF-7cells in G2/M and activate JNK and p38signal pathway while inhibit theactivation of ERK signal pathway and downregulate Bcl-2pathway.