Pro-Apoptosis Effects of Yangzheng-Xiaoji Capsules in Hepatocellular Carcinoma: Activation of the p53-Induced Apoptotic Pathway and Inhibition of the PI3K/Akt Pathway.

Background: Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, characterized by high incidence and mortality rates. Yangzheng-Xiaoji capsules (YXC) have been widely used in Traditional Chinese Medicine for the treatment of HCC in China; however, the composition of compounds in YXC and its underlying anti-tumor mechanisms remain unclear.

Methods: High-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) was used to analyze the composition of YXC. An MHCC97H orthotopic mouse model of HCC was used to assess the therapeutic efficacy of YXC and its impact on the p53-induced apoptotic pathway and the PI3K/Akt pathway. YXC-mediated serum was prepared, and its optimal intervention concentration was determined using the MTT assay. The effects of YXC-mediated serum on apoptosis in MHCC97H cells, as well as on the p53-induced apoptotic pathway and the PI3K/Akt pathway, were investigated and verified through the TUNEL assay.

Results: HPLC-Q-TOF-MS/MS analysis identified 58 components in YXC. In vivo, YXC significantly improved body weight, dietary status, survival rate, and tissue pathology, inhibited xenografts growth, promoted apoptosis of HCC cells, activated the p53-induced apoptotic pathway, and inhibited the PI3K/Akt signaling pathway with good safety. In vitro, YXC-mediated serum showed similar efficacy. When 20% YXC-mediated serum was added to MHCC97H cells, the increased apoptosis was significantly rescued by the addition of p53 inhibitor (PFT-α) or PI3K activator (740Y-P).

Conclusion: The results of this study indicate that YXC exhibits anti-proliferative and pro-apoptotic pharmacological activity via activating the p53-induced apoptotic pathway and suppressing the PI3K/Akt pathway.