Sorafenib is currently used to treat
hepatocellular carcinoma (HCC). However, the development of chemoresistance to
sorafenib is a major limitation for
sorafenib-based
therapy in patients with HCC. In the present study, the effect of the combination
therapy of
sorafenib and wh-4 on the proliferation of
liver cancer cells was investigated. The results showed that
sorafenib with wh-4 additively suppressed the proliferation of
liver cancer cells. The colony formation of
liver cancer cells decreased significantly in response to the combination treatment of
sorafenib with wh-4, and it also induced the apoptosis of
liver cancer cells. Western blot analysis demonstrated decreased expression of Bcl2, and increased expression of Bax in
liver cancer cells treated with a combination of
sorafenib and wh-4. Moreover, the migration of
liver cancer cells was inhibited. The combination treatment of
sorafenib with wh-4 reduced the expression levels of ABCB1 and ABCG2 which are responsible for resistance. Finally, STAT3 overexpression abolished the proliferation inhibition effect of
sorafenib with wh-4 on
liver cancer cells, and
sorafenib and wh-4 suppressed the proliferation of
liver cancer cells by STAT3 pathway. Together, these results suggest that sorafenib-wh4 combination treatment is a potential novel therapeutic approach to suppress the proliferation of
liver cancer cells.