Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo
Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo
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DOI：
10.1111/j.1349-7006.2011.01916.x
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发表时间：
2011-06-01
期刊：
影响因子：
5.7
通讯作者：
Okayasu, Ryuichi
中科院分区：
文献类型：
--
作者：
Anzai, Kazunori;Sekine-Suzuki, Emiko;Okayasu, Ryuichi
ZSTK474是一种新型口服磷酸肌苷3-激酶特异性抑制剂，能有效抑制癌细胞增殖。为了进一步探索ZSTK474的抗肿瘤作用，为今后的临床应用提供参考，我们研究了ZSTK474与放疗的联合作用。x射线或ZSTK474均能抑制HeLa细胞的增殖。x射线联合治疗后，ZSTK474口服8天，照射后24 h开始，明显增强细胞生长抑制作用。对连续ZSTK474治疗的克隆性存活也观察到联合效应。Western blot分析显示，x照射可增强Akt和GSK-3 β的磷酸化，而ZSTK474单独处理可抑制磷酸化。x射线照射后用ZSTK474治疗也能抑制磷酸化，并显著抑制异种移植瘤的生长。x射线和ZSTK474联合治疗在体外和体内都比单独放疗或药物治疗具有更大的治疗潜力。[j] .癌症科学，2011;32(2):1176-1180。
ZSTK474 is a novel orally applicable phosphoinositide 3-kinase-specific inhibitor that strongly inhibits cancer cell proliferation. To further explore the antitumor effect of ZSTK474 for future clinical usage, we studied its combined effects with radiation. The proliferation of HeLa cells was inhibited by treatment with X-rays alone or ZSTK474 alone. Combination treatment using X-rays then ZSTK474 given orally for 8 days, starting 24 h post-irradiation, significantly enhanced cell growth inhibition. The combined effect was also observed for clonogenic survival with continuous ZSTK474 treatment. Western blot analysis showed enhanced phosphorylation of Akt and GSK-3 beta by X-irradiation, whereas phosphorylation was inhibited by ZSTK474 treatment alone. Treatment with ZSTK474 after X-irradiation also inhibited phosphorylation, and remarkably inhibited xenograft tumor growth. Combined treatment with X-rays and ZSTK474 has greater therapeutic potential than radiation or drug therapy alone, both in vitro and in vivo. (Cancer Sci 2011; 102: 1176-1180).