Combination treatment with sorafenib and wh‑4 additively suppresses the proliferation of liver cancer cells

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.