丹参酮Ⅰ对Lewis肺癌荷瘤小鼠放射增敏作用及机制研究

Radiosensitizing Effect and Mechanism of Tanshinone Ⅰ in Mice Bearing Lewis Lung Carcinoma

目的探讨丹参酮Ⅰ(tanshinoneⅠ,TanⅠ)联合照射对Lewis肺癌荷瘤小鼠的抑瘤作用、放射增敏作用及其机制。方法通过接种Lewis肺癌细胞建立C57BL/6小鼠Lewis肺癌移植瘤模型,随机分为空白对照组、单纯照射组、单丹参酮Ⅰ(40mg·kg-1)给药组、单氟尿嘧啶对照组、氟尿嘧啶联合照射组、丹参酮Ⅰ(10、20、40 mg·kg-1)联合照射组。经照射后,计算肿瘤相对体积、肿瘤生长延缓时间和增敏系数(enhancement factor,EF);剥瘤称重,计算抑瘤率;TUNEL法检测组织的凋亡情况。免疫蛋白印记法(Western blot)检测Bcl-2和Bax蛋白的表达。结果不同剂量的丹参酮Ⅰ(低、中、高)联合照射均能抑制肿瘤生长,其抑瘤率分别为27.14%、38.46%、59.78%,显著高于单照射组(P<0.01),并具有较好的放射增敏作用,其增敏比分别为1.09、1.76、2.03。丹参酮Ⅰ高剂量联合照射组可见细胞皱缩,凋亡指数(apoptosis index,AI)为51.3%,显著高于单照射组(P<0.05)。丹参酮Ⅰ联合照射能下调Bcl-2蛋白表达,并上调Bax蛋白表达。结论丹参酮Ⅰ联合照射后对Lewis肺癌荷瘤小鼠具有一定的抑瘤作用和放射增敏作用,可能通过Bcl-2/Bax蛋白的调控,诱导细胞凋亡发挥增敏作用。

OBJECTIVE To investigate the mechanism of inhibition and radiosensitization effects of combining treatment with tan- shinone I and（irradiation） IR on mice bearing Lewis lung carcinoma（LLC）. METHODS The models of LLC in C57BL/6 mice were established via subcutaneous injection of mouse LLC cells, and divided into model control group, radiation alone group, Tan I （40 mg · kg-1 ） group, 5-Fu ＋ IR group, Tan I （ 10,20,40 mg· kg^-1 ） ＋ IR groups. After irradiated, the relative volume of tumor was observed, the delay time of tumor growth and enhancement factor（EF） was calculated. After stripped, the inhibition rate was calculat- ed. Cell apoptosis index（AI） was in vestigated by TUNEL staining. The protein expressions of Bcl-2 and Bax were detected by West- ern blot. RESULTS The different concentrations of Tan I （ low, medium and high） ＋ IR groups inhibited the tumor growth signifi- cantly, and the inhibition rate was 27. 14% , 38.46% ,59. 78% , respectively, which were significant difference as compared with IR group （ P 〈 0. 01 ）. And also had the significant radiosensitizing effect, the enhancement factor was 1.09,1.76,2.03, respectively. The AI was 51.3 % in Tan I （H） ＋ IR group, which was significant difference as compared with IR group（ P 〈 0. 05 ）. The expression of Be1-2 protein was decreased, and Bax proteins was increased by combining treatment with Tan I and IR. CONCLUSION Combining treatment with Tan I and IR inhibited the tumor growth and had radiosensitizing effects in mice bearing LLC. One of the mechanism may be that it might induce apoptosis by regulated the expression of Bcl-2/ Bax protein, so cells were more sensitive to radiation.