Zhang Chao, Qiu Xingsheng
Radiation Oncology Department, Panyu Central Hospital, Guangzhou, China.
Cancer Institute of Panyu, Guangzhou, 510120, China.
Tumour Biol. 2015 Nov;36(11):8359-65. doi: 10.1007/s13277-015-3578-9. Epub 2015 May 28.
Andrographolide (AND), a diterpenoid lactone isolated from Andrographis paniculata, has been shown to have radiosensitivity in several types of cancer. Whether AND can radiosensitize ovarian cancer remains unknown. The present study investigated the radiosensitizing effects of AND in human ovarian SKOV3 xenografts and examined the molecular mechanisms of AND-mediated radiosensitization. Nude mice bearing human ovarian SKOV3 were treated with AND to investigate the effects of drug administration on tumor growth, radiosensitivity, apoptosis, and autophagy. Subsequent Western blot analysis and monodansylcadaverine (MDC) staining (autophagy analysis) were used to determine the role of AND. Finally, the pathway of apoptosis was characterized by caspase-3 activity assay as well as TUNEL analysis. AND potently sensitized SKOV3 xenografts to radiation. Moreover, apoptosis and autophagy in radiation combined with drug-treated xenografts increased significantly compared with the simple drug or single radiation treatment. This result was associated with an increase in the Bax/Bcl-2 protein ratio and p-p53 expression after exposure to combination treatment. Meanwhile, the level of Beclin 1 and Atg5 and the conversion from LC3-I to LC3-II, three important proteins involved in autophagy, were increased. AND acts as a strong radiosensitizer in human ovarian SKOV3 xenografts in vivo by increasing the Bax/Bcl-2 protein ratio and promoting the activation of caspase-3, leading to enhanced apoptosis as well as autophagy.
穿心莲内酯（AND）是从穿心莲中分离出的一种二萜内酯，已被证明在几种类型的癌症中具有放射敏感性。AND是否能使卵巢癌产生放射增敏作用仍不清楚。本研究调查了AND对人卵巢SKOV3异种移植瘤的放射增敏作用，并探讨了AND介导放射增敏作用的分子机制。用人卵巢SKOV3移植瘤的裸鼠接受AND治疗，以研究给药对肿瘤生长、放射敏感性、凋亡和自噬的影响。随后采用蛋白质免疫印迹分析和单丹磺酰尸胺（MDC）染色（自噬分析）来确定AND的作用。最后，通过半胱天冬酶-3活性测定以及TUNEL分析来表征凋亡途径。AND能有效地使SKOV3异种移植瘤对辐射敏感。此外，与单纯药物治疗或单一放疗相比，放疗联合药物治疗的异种移植瘤中的凋亡和自噬显著增加。这一结果与联合治疗后Bax/Bcl-2蛋白比值和p-p53表达的增加有关。同时，参与自噬的三种重要蛋白质Beclin 1和Atg5的水平以及从LC3-I到LC3-II的转化均增加。AND通过增加Bax/Bcl-2蛋白比值并促进半胱天冬酶-3的激活，在体内对人卵巢SKOV3异种移植瘤起到强大的放射增敏作用，从而导致凋亡和自噬增强。
