Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai, China.
School of Physical Education & Health Care, East China Normal University, Shanghai, China.
Clin Exp Pharmacol Physiol. 2021 Sep;48(9):1239-1250. doi: 10.1111/1440-1681.13536. Epub 2021 Jun 23.
The anti-tumour effects of exercise are still poorly understood. In recent years, high-intensity interval exercise has been recognised as one of the best choices for better health. However, high-intensity interval exercise induces lactate production in muscles and elevates blood lactic acid levels, and the resulting acidic microenvironment may promote tumour progression. Therefore, it is important to compare the anti-tumour effects of different types of exercise.
In this study, we aimed to compare the anti-tumour effects of moderate endurance training and high-intensity interval training on diethylnitrosamine (DEN)-induced liver tumours and to explore the underlying mechanisms.
Three-week-old male C57BL/6 mice were injected intraperitoneally with DEN for 10 weeks to induce hepatocellular carcinoma. DEN-treated mice were grouped and subjected to moderate endurance training (MET) or high-intensity interval training (HIIT) for 18 weeks. We performed real-time PCR to evaluate the mRNA expressions of key enzymes involved in lactate metabolism pathway and western blotting to examine the protein expressions of LDHA, AMPK/P-AMPK, PCK1, and G6Pase in the paracancerous liver tissue. We performed high-performance liquid mass spectrometry (HPLC) to detect lactate in liver.
Our results revealed that compared with HIIT, MET decreased hepatic tumour incidence, as HIIT increased blood lactate concentration at rest. Moreover, MET reduced the transcript-level expression of LDH subunit and significantly increased the mRNA levels of COX1 and ND1 in liver. However, no significant changes were observed in liver lactate levels and the expression of LDHA among the groups. In addition, no significant differences in the mRNA levels of critical enzymes involved in the gluconeogenesis pathway in liver were observed among the groups. Additionally, no significant differences were observed in the mRNA levels of MPC2, pdha2, and pdk4 among the groups.
Our findings suggest that MET may be more efficient than HIIT at reducing hepatic tumourigenesis, and that it is associated with improved mitochondrial function in liver and lower lactate load in the circulation at rest.
运动的抗肿瘤作用仍知之甚少。近年来，高强度间歇训练已被认为是促进健康的最佳选择之一。然而，高强度间歇训练会在肌肉中引起乳酸的产生，并使血液中的乳酸水平升高，而由此产生的酸性微环境可能会促进肿瘤的进展。因此，比较不同类型运动的抗肿瘤作用非常重要。
本研究旨在比较中等耐力训练和高强度间歇训练对二乙基亚硝胺（DEN）诱导的肝肿瘤的抗肿瘤作用，并探讨其潜在机制。
3 周龄雄性 C57BL/6 小鼠经腹腔注射 DEN 10 周，诱导肝细胞癌。用 DEN 处理的小鼠分组，进行 18 周的中等耐力训练（MET）或高强度间歇训练（HIIT）。我们进行实时 PCR 评估关键酶的 mRNA 表达涉及乳酸代谢途径和 Western blot 检测 LDHA、AMPK/P-AMPK、PCK1 和 G6Pase 在癌旁肝组织中的蛋白表达。我们进行高效液相质谱（HPLC）检测肝乳酸。
与 HIIT 相比，MET 降低了肝肿瘤的发生率，因为 HIIT 增加了休息时的血液乳酸浓度。此外，MET 降低了 LDH 亚基的转录水平表达，并显著增加了肝中 COX1 和 ND1 的 mRNA 水平。然而，各组之间的肝乳酸水平和 LDHA 的表达没有明显变化。此外，各组之间肝内糖异生途径关键酶的 mRNA 水平无显著差异。此外，各组之间 MPC2、pdha2 和 pdk4 的 mRNA 水平无显著差异。
我们的研究结果表明，MET 可能比 HIIT 更有效地降低肝肿瘤发生，这与改善肝线粒体功能和休息时循环中乳酸负荷降低有关。
