Pien Tze Huang inhibits tumor cell proliferation and promotes apoptosis via suppressing the STAT3 pathway in a colorectal cancer mouse model

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in cell survival and proliferation. Constitutive activation of STAT3 is strongly correlated with pathogenesis of various types of malignant tumors including colorectal cancer (CRC), and therefore is a major focus in the development of anti-cancer agents. Pien Tze Huang (PZH), a well-known traditional Chinese formula prescribed already in the Ming Dynasty, has been demonstrated to be clinically effective in the treatment of CRC. However, the precise mechanism of its anti-cancer activity remains largely unknown. In the present study we evaluated the efficacy of PZH against tumor growth in vivo in the CRC mouse xenograft model, and investigated the underlying molecular mechanisms. We found that administration of PZH reduced tumor volume and tumor weight but had no effect on body weight gain in CRC mice, demonstrating that PZH can inhibit colon cancer growth in vivo without apparent adverse effect. We also observed that PZH treatment inhibited the phosphorylation level of STAT3 in tumor tissues. Consequently, the inhibitory effect of PZH on STAT3 activation resulted in the up-regulation of Bax/Bcl-2 ratio as well as down-regulation of Cyclin D1 and CDK4 expression, leading to the induction of apoptosis as well as the inhibition of cell proliferation. These results suggest that promotion of cancer cell apoptosis and inhibition of proliferation via suppression of STAT3 pathway might be one of the mechanisms by which PZH treats colorectal cancer.