Chun Yong Jin, Park In Chul, Park Myung Jin, Woo Sang Hyeok, Hong Seok Il, Chung Hee Yong, Kim Tae Hwan, Lee Yun Sil, Rhee Chang Hun, Lee Su Jae
Laboratory of Radiation Effect, Korea Cancer Center Hospital, Gongneung-Dong, Nowon-Ku, Seoul, South Korea.
FEBS Lett. 2002 May 22;519(1-3):195-200. doi: 10.1016/s0014-5793(02)02765-5.
Arsenic trioxide (As2O3) inhibits cell growth and induces apoptosis in certain types of cancer cells including acute promyelocytic leukemia, prostate and ovarian carcinomas, but its effect on response of tumor cells to ionizing radiation has never been explored before. Here we demonstrate that As2O3 can sensitize human cervical cancer cells to ionizing radiation both in vitro and in vivo. As2O3 in combination with ionizing radiation have a synergistic effect in decreasing clonogenic survival and in the regression of established human cervical tumor xenografts. Pretreatment of the cells with As2O3 also synergistically enhanced radiation-induced apoptosis. Apoptosis of the cells by combined treatment of As2O3 and radiation was associated with reactive oxygen species generation and loss of mitochondrial membrane potential, resulting in the activation of caspase-9 and caspase-3. The combined treatment also resulted in an increased G2/M cell cycle distribution at the concentration of As2O3 which did not alter cell cycle when applied alone. These results indicate that As2O3 can synergistically enhance radiosensitivity of human cervix carcinoma cells in vitro and in vivo, suggesting a potential clinical applicability of combination treatment of As2O3 and ionizing radiation in cancer therapies.
三氧化二砷（As2O3）可抑制某些类型癌细胞（包括急性早幼粒细胞白血病、前列腺癌和卵巢癌）的细胞生长并诱导其凋亡，但此前从未探究过其对肿瘤细胞对电离辐射反应的影响。在此我们证明，As2O3在体外和体内均可使人类宫颈癌细胞对电离辐射敏感。As2O3与电离辐射联合使用在降低克隆形成存活率以及使已建立的人类宫颈肿瘤异种移植瘤消退方面具有协同作用。用As2O3对细胞进行预处理还可协同增强辐射诱导的细胞凋亡。As2O3与辐射联合处理导致的细胞凋亡与活性氧生成及线粒体膜电位丧失有关，进而导致半胱天冬酶-9和半胱天冬酶-3激活。联合处理在As2O3浓度下还导致G2/M期细胞周期分布增加，而该浓度的As2O3单独应用时不会改变细胞周期。这些结果表明，As2O3在体外和体内均可协同增强人类宫颈癌细胞的放射敏感性，提示As2O3与电离辐射联合治疗在癌症治疗中具有潜在的临床应用价值。
