Buchwald H
Department of Surgery, UMHC, University of Minnesota, Minneapolis 55455.
Lancet. 1992 May 9;339(8802):1154-6. doi: 10.1016/0140-6736(92)90744-n.
An important feature of malignant transformation is loss of the cholesterol feedback inhibition mechanism that regulates cholesterol synthesis. Cancer cells seem to require an increase in the concentrations of cholesterol and of cholesterol precursors. Therefore, a reasonable assumption is that prevention of tumour-cell growth can be achieved by restricting either cholesterol availability or cholesterol synthesis. In-vivo and cell-culture experiments have shown that lowering the plasma cholesterol concentration or intervening in the mevalonate pathway with 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitors decreases tumour growth. Currently prescribed doses of HMG-CoA reductase inhibitors given orally or continuously by an implantable infusion pump could achieve tumour therapeutic tissue concentrations of these agents. My hypothesis is that cholesterol inhibition can inhibit tumour cell growth, can act as an adjuvant to cancer chemotherapy, and, possibly, can prevent carcinogenesis.
恶性转化的一个重要特征是调节胆固醇合成的胆固醇反馈抑制机制丧失。癌细胞似乎需要增加胆固醇及其前体的浓度。因此，一个合理的假设是，通过限制胆固醇的供应或胆固醇的合成，可以实现对肿瘤细胞生长的抑制。体内和细胞培养实验表明，降低血浆胆固醇浓度或用3-羟基-3-甲基戊二酰辅酶A（HMG）还原酶抑制剂干预甲羟戊酸途径可减少肿瘤生长。目前通过口服或植入式输液泵持续给予的HMG-CoA还原酶抑制剂剂量可使这些药物在肿瘤治疗组织中达到有效浓度。我的假设是，抑制胆固醇可以抑制肿瘤细胞生长，可作为癌症化疗的辅助手段，并且可能预防癌症发生。
