Oxygenation inhibits ovarian tumor growth by downregulating STAT3 and cyclin-D1 expressions
Oxygenation inhibits ovarian tumor growth by downregulating STAT3 and cyclin-D1 expressions
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DOI：
10.4161/cbt.10.4.12448
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发表时间：
2010-08-15
影响因子：
3.6
通讯作者：
Kuppusamy, Periannan
中科院分区：
文献类型：
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作者：
Selvendiran, Karuppaiyah;Kuppusamy, M. Lakshmi;Kuppusamy, Periannan
缺氧是许多实体肿瘤中常见的现象，是化疗或放射治疗的主要障碍。低氧也被认为过度表达/激活信号转导和转录激活因子3(STAT3)，导致肿瘤进展和耐药。我们推测，缺氧肿瘤的氧合增加可能对STAT3的激活有抑制作用，从而抑制肿瘤生长。携带人卵巢癌异种移植瘤的小鼠每天暴露在高压氧(HBO；100%氧气；2atm；持续90分钟)中，持续21天。暴露在高压氧下的小鼠肿瘤体积显著缩小，对体重没有影响。高压氧暴露使STAT3(Tyr705)活性和细胞周期蛋白-D1mRNA水平显著降低。有趣的是，HBO暴露，结合每周一次的顺铂给药，也显著减少了肿瘤体积；然而，与其他组相比，这组小鼠的体重显著减轻。虽然传统的观点可能认为增加肿瘤的氧合会促进肿瘤的生长，但本研究的结果表明并非如此。高氧似乎抑制了STAT3的激活，这是卵巢肿瘤进展的关键步骤。本研究对卵巢癌的临床治疗有重要意义。
Hypoxia, which is commonly observed in many solid tumors, is a major impediment to chemo- or radiation therapy. Hypoxia is also known to overexpress/activate signal transducer and activator of transcription 3 (STAT3) leading to tumor progression as well as drug resistance. We hypothesized that increased oxygenation of the hypoxic tumor may have an inhibitory effect on STAT3 activation and hence tumor-growth inhibition. Mice containing human ovarian cancer xenograft tumor were exposed to hyperbaric oxygen (HBO; 100% oxygen; 2 atm; 90-min duration) daily, for up to 21 days. Mice exposed to HBO showed a significant reduction in tumor volume, with no effect on body weight. STAT3 (Tyr 705) activation and cyclin-D1 protein/mRNA levels were significantly decreased up on HBO exposure. Interestingly, HBO exposure, in combination with weekly administration of cisplatin, also significantly reduced the tumor volume; however, this group of mice had drastically reduced body weight when compared to other groups. While conventional wisdom might suggest that increased oxygenation of tumors would promote tumor growth, the results of the present study indicated otherwise. Hyperoxia appears to inhibit STAT3 activation, which is a key step in the ovarian tumor progression. The study may have important implications for the treatment of ovarian cancer in the clinic.