质子泵抑制剂与肿瘤耐药研究

Studies of proton pump inhibitors and tumor resistance to antitumor drugs

恶性肿瘤对抗癌药物的耐药性是肿瘤患者治疗失败的主要原因。肿瘤细胞外微环境的高度酸化是肿瘤细胞对化疗药物产生耐药的机制之一。改变肿瘤细胞内外的pH梯度是逆转耐药的一种有效方法。作为抗酸剂治疗胃病的质子泵抑制剂能够通过抑制质子泵的功能,改变pH梯度而阻断肿瘤微环境的酸化,达到提高肿瘤对化疗药物敏感性的目的。

Resistance to antitumor agents is a major cause of treatment failure in patients with cancer. Some mechanisms of tumor resistance to cytotoxic drugs may involve increased acidification of extracellular compartments. An option to revert multi-drug resistance is the use of agents that disrupt the pH gradient between the extracellular environment and the cell cytoplasm in tumours. Proton pump inhibitors （PPIs）, a class of V-H^＋-ATPase inhibitors and currently used in the anti-acid treatment of peptic disease, could inhibit the acidification of the tumor microenvironment and increase the sensitivity of tumor cells to cytotoxic agents by inhibiting the function of pumps generating the pH gradient.