van den Bogert C, Dontje B H, Kroon A M
Cancer Res. 1983 May;43(5):2247-51.
Oxytetracycline was given by means of chronic i.v. infusion, in amounts which impair specifically mitochondrial protein synthesis, to Wistar rats carrying a solid Leydig cell tumor. The prolonged inhibition of mitochondrial protein synthesis finally results in proliferation arrest of the s.c. growing tumor. As long as the tumor is growing, the energy-generating capacity of the mitochondrial becomes diluted, until it is reduced to a critical level, which results in growth arrest. This cytostatic effect is found after treatment for 8 to 12 days. During this period, the tumor volume increases to an extent comparable to 2 to 3 tumor cell divisions. The proliferation arrest found is, at least after treatment for 3 weeks, reversible. Withdrawal of oxytetracycline results in continuation of tumor growth after a latent period of about 5 days. The data confirm previous observations made in experimental systems about the usefulness of mitochondrial protein synthesis as target for cancer chemotherapy. They support, moreover, the explanation given for the marked prolongation of survival time found in tetracycline-treated patients with a squamous cell carcinoma of the larynx-pharynx. If antineoplastic therapy, based on inhibition of mitochondrial protein synthesis, is considered, the tetracyclines should be the drugs of choice, because their toxic side effects are minimal at dosages which cause tumor proliferation arrest.
对携带实体性睾丸间质细胞瘤的Wistar大鼠，通过慢性静脉输注给予土霉素，剂量足以特异性损害线粒体蛋白质合成。线粒体蛋白质合成的长期抑制最终导致皮下生长肿瘤的增殖停滞。只要肿瘤在生长，线粒体的能量生成能力就会被稀释，直至降至临界水平，从而导致生长停滞。这种细胞抑制作用在治疗8至12天后出现。在此期间，肿瘤体积增加到相当于2至3次肿瘤细胞分裂的程度。至少在治疗3周后发现的增殖停滞是可逆的。停用土霉素后，约5天的潜伏期后肿瘤继续生长。这些数据证实了先前在实验系统中关于线粒体蛋白质合成作为癌症化疗靶点的有用性的观察结果。此外，它们支持了对四环素治疗的喉咽鳞状细胞癌患者生存时间显著延长的解释。如果考虑基于抑制线粒体蛋白质合成的抗肿瘤治疗，四环素应是首选药物，因为在导致肿瘤增殖停滞的剂量下，它们的毒副作用最小。
