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目的研究肌醇六磷酸(IP6)对HT-29细胞裸鼠皮下移植瘤生长的抑制作用。方法建立HT-29细胞裸鼠移植瘤模型,随机分为4组,对照组,5-氟尿嘧啶组(5-FU)组,IP6低剂量组,IP6高剂量组。每组8只。每组每日腹腔注射1次0.5ml;分别含生理盐水,5-FU20mg/kgbw,IP640mg/kgbw,100mg/kgbw。用药20d后经颈椎脱位处死。比较各组抑瘤作用和裸鼠一般状态的变化,对标本分别行光镜和电镜观察、Hoechst染色、原位末端标记(TUNEL)和免疫组化检测。结果生理盐水,低、高IP6及5-FU组瘤重分别为0.68±0.31、0.57±0.28、0.58±0.18、0.24±0.23g;瘤体积分别为0.71±0.35、0.58±0.21、0.59±0.20和0.34±0.27cm3;与对照组比,5-FU组瘤量、瘤体积显著降低(P<0.05),IP6组瘤重和体积呈一定降低趋势,但无显著差异(P>0.05)。免疫组化检测显示,与对照组比,低、高IP6组P53蛋白表达显著降低(P<0.05),PCNA表达无显著差异(P>0.05)。TUNEL检测结果,与对照组比,低、高IP6组细胞凋亡率显著升高(P<0.05)。结论IP6可能通过抑制P53表达、诱导肿瘤细胞凋亡,而起到抑制和延缓肿瘤生长的作用。
Objective To study the inhibitory effect of phytate (IP6) on the growth of subcutaneously transplanted HT-29 cells in nude mice. Methods The nude mice model of HT-29 cells was established and randomly divided into 4 groups: control group, 5-fluorouracil group (5-FU) group, IP6 low dose group and IP6 high dose group. Each group of 8. Each group of intraperitoneal injection 0.5ml once daily; saline, 5-FU20mg / kgbw, IP640mg / kgbw, 100mg / kgbw. 20d after treatment by cervical dislocation. The antitumor effects of each group and the general state of nude mice were compared. The specimens were examined by light and electron microscopy, Hoechst staining, TUNEL and immunohistochemistry respectively. Results The tumor weights in saline, low and high IP6 and 5-FU groups were 0.68 ± 0.31, 0.57 ± 0.28, 0.58 ± 0.18 and 0.24 ± 0.23g respectively; the tumor volumes were 0.71 ± 0.35, 0.58 ± 0.21 and 0.59 ± 0.20 and 0.34 ± 0.27cm3. Compared with the control group, the tumor volume and tumor volume of 5-FU group were significantly decreased (P <0.05). The tumor weight and volume of IP6 group showed a trend of decreasing but no significant difference (P> 0.05). Immunohistochemistry showed that compared with the control group, the expression of P53 protein in low and high IP6 groups was significantly lower (P <0.05) and PCNA expression was not significantly different (P> 0.05). The results of TUNEL assay showed that compared with the control group, the apoptotic rates in low and high IP6 groups were significantly increased (P <0.05). Conclusion IP6 may inhibit and delay tumor growth by inhibiting the expression of P53 and inducing tumor cell apoptosis.