Role of apoptosis and autophagy in chemoradiotherapy for hepatocellular carcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15950
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: The University of Tokushima
• Principal Investigator: TANAKA Hironori 徳島大学, 病院, 医員 (40792388)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 肝細胞癌 / ミリプラチン / 放射線療法 / 相乗効果

Outline of Final Research Achievements

We investigated anti-cancer activity including synergistic effect of MPT and radiation combination using HCC cells and the mechanism of apoptosis induction. Human HCC cell lines HepG2 and HuH-7 were treated with DPC (active form of MPT) and X-ray irradiation, and synergistic effect was evaluated using combination index (CI). Combination of DPC and irradiation decreased cell viability. The CI was <1 in both cell lines, indicating their synergistic effect against HCC cells. Expression of apoptosis-related proteins was analyzed by Western blotting. Treatment with DPC and X-ray irradiation induced cleaved PARP much more strongly, suggesting their synergistic effect on apoptosis. expression level of PUMA was significantly increased in the combination group of both cell lines. Our data suggested that the combination with MPT and radiation showed their synergistic effect on apoptosis induction in HCC cells and that PUMA played an important role in apoptosis.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

これまで肝癌における化学療法と放射線療法の併用による相乗効果の有無については十分に解明されていなかった。今回、我々の研究では抗癌剤ミリプラチンと放射線の併用により相乗効果が示され、その機序としてアポトーシス誘導が示唆された。脈管浸潤を伴う肝癌の予後は極めて不良であり、その理由として既存の治療での奏効率が低いことが挙げられている。ミリプラチン併用化学放射線療法の相乗効果が示されたことにより、今後は進行肝癌の治療選択肢が増えることにつながると考えらえる。