Possible Interaction: Tretinoin and Sorafenib

“Moreover, ATRA also synergistically enhanced the ability of sorafenib to reduce Pin1 and inhibit tumor growth of HCC in mouse xenograft models.”

“Furthermore, all‐trans retinoic acid decreased AKT activity, reduced the epithelial cell adhesion molecule–positive cell population enriched by sorafenib , and potentiated the therapeutic effect of sorafenib in the patient‐derived xenograft model.”

“Cell viability assays in six HCC cell lines, HepG2, PLC/PRF/5, HuH6, HLE, HLF, and Hep3B, revealed that 5 and 10 μM ATRA , concentrations that do not exert cytotoxic effects, enhanced the cytotoxicity of sorafenib , being much more effective than NIK‐333 and Am80.”

“In the combination treatment using ATRA and sorafenib , increased apoptosis, followed by the activation of p38 MAPK and JNK, the upregulation and translocation of Bax to mitochondria, and the activation of caspase‐3, was observed.”

“Our results thus indicate that ATRA is useful for enhancing the cytotoxicity of sorafenib against HCC cells by regulating the energy metabolism of HCC cells.”

“ Sorafenib blocks ATRA-induced Mcl-1 increase by reversing p90RSK activation and GSK3β inactivation, maintains the repressed Bcl-2 level, and enhances ATRA induced apoptosis in non-APL AML cell lines and in primary AML cells.”

“In the present study, we investigated in vitro whether ATRA modulates the response of human hepatocellular carcinoma (HCC) cells to sorafenib , the only proven oral drug for advanced HCC, and the underlying mechanisms.”

“Thus, a connexin-dependent gap junction enhancement may play a central role in ATRA plus sorafenib synergy in inhibiting HCC cell growth.”

“Whereas lower concentrations of sorafenib (5 μM) or ATRA (0.1 or 10 μM) alone modestly induced GJIC activity, the combination of sorafenib plus ATRA resulted in a strong enhancement of GJIC.”

“Moreover, when sorafenib was added along with retinoic acid and forskolin, apoptosis was increased, suggesting that anti-fibrosis drugs may improve tissue penetration to support the efficacy of anti-cancer drugs.”