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目的研究吲哚新碱(new indole alkali,NIA)对S180肉瘤细胞小鼠皮下移植瘤的抑制作用及其机制。方法建立S180肉瘤细胞小鼠皮下移植瘤动物模型,随机分为空白对照组(溶剂灌胃组)、阳性对照组(CTX,50mg.kg-1.d-1)及NIA低剂量组、中剂量组、高剂量组。观察小鼠体质量变化并计算抑瘤率;观察肿瘤组织病理学变化;用免疫组化法检测移植瘤组织中Bax及Survivin蛋白表达,并用TUNEL法检测细胞凋亡。结果与空白对照组比较,CTX组及NIA低、中、高剂量组肿瘤生长均比较缓慢,瘤质量差异有统计学意义(P均<0.05),抑瘤率分别为53.48%、19.67%、23.45%、37.06%;与CTX组比较,NIA低、中、高剂量组瘤质量较大,差异均有统计学意义(P均<0.05)。病理组织学检查,NIA组标本可见细胞凋亡形态变化。与空白对照组比较,CTX组及NIA高、中剂量组Bax蛋白表达及凋亡指数增高,CTX组及NIA高剂量组Survivin蛋白表达下调,差异均有统计学意义(P均<0.05)。与CTX组比较,NIA高、中、低剂量组Bax蛋白表达及凋亡指数降低(P均<0.05),NIA低、中剂量组Survivin蛋白表达上凋(P均<0.05)。结论NIA对小白鼠S180细胞皮下移植瘤有明显抑瘤作用,其抑瘤机制与诱导S180细胞凋亡有关。
Objective To study the inhibitory effect and mechanism of new indole alkali (NIA) on subcutaneous xenografts in S180 sarcoma mice. Methods The subcutaneous xenografts in S180 sarcoma mice were established and randomly divided into blank control group (solvent-fed group), positive control group (CTX, 50mg.kg-1.d-1) and NIA low dose group Group, high dose group. The changes of body weight were observed and the tumor inhibition rate was calculated. The histopathological changes of tumor were observed. The expression of Bax and Survivin protein in tumor tissue were detected by immunohistochemistry. Cell apoptosis was detected by TUNEL. Results Compared with the blank control group, the tumor growth of CTX group and NIA low, middle and high dose groups were relatively slow, the tumor mass difference was statistically significant (P <0.05), the tumor inhibition rates were 53.48%, 19.67%, 23.45 % And 37.06%, respectively. Compared with CTX group, the tumor mass of low, medium and high dose NIA group was larger, the differences were statistically significant (all P <0.05). Histopathological examination, NIA group of specimens showed morphological changes of apoptosis. Compared with the blank control group, the expression of Bax protein and apoptosis index in CTX group and NIA high and middle dose groups were increased, and the expression of Survivin protein in CTX group and NIA high dose group was significantly lower than that in control group (all P <0.05). Compared with CTX group, the expression of Bax protein and apoptosis index in NIA group were lower than those in NIA group (all P <0.05). Survivin protein expression in low and middle dose NIA group was significantly higher than that in CTX group (all P <0.05). Conclusion NIA has obvious anti-tumor effect on the subcutaneous transplantation of S180 cells in mice and its anti-tumor mechanism is related to the induction of S180 cell apoptosis.