白芥子挥发油对小鼠肝癌H_(22)移植性肿瘤的抑制作用及其机制研究

Antitumor effect of volatile oil from Sinapis Albae Semen on H_(22)-bearing mice and its mechanism

目的探讨白芥子挥发油对肝癌H22移植性肿瘤的抑制作用及其机制。方法建立小鼠肝癌H22移植性肿瘤模型。造模24 h后小鼠分成5组:模型组,环磷酰胺(25 mg/kg)阳性对照组,白芥子挥发油低、中、高剂量(20、40、80 mg/kg)组,采用腹腔给药或原位注射给药,观察白芥子挥发油对H22荷瘤小鼠肿瘤质量、生存期的影响;HE染色法以及吖啶橙(AO)染色观察肿瘤细胞形态的变化;免疫组化法检测肿瘤细胞凋亡相关蛋白Bax、Bcl-2的表达。结果白芥子挥发油显著延长H22荷瘤小鼠生存期并抑制肿瘤生长(P<0.01);上调Bax的表达、下调Bcl-2的表达。白芥子挥发油对H22细胞的抑制作用呈良好的剂量相关性,但高剂量组毒副作用明显。结论白芥子挥发油能够抑制H22荷瘤小鼠肿瘤细胞的生长,其机制可能与上调Bax的表达、下调Bcl-2的表达,进而诱导细胞凋亡有关。

Objective To investigate the antitumor effect of volatile oil from Sinapis Albae Semen （VOSAS） on H22-bearing mice andto determine the mechanism. Methods To establish the H22 implanted hepatocellular carcinoma animal model which was used to analyze the effect of VOSAS on the growth of transplanted tumor. Mice were divided into five groups 24 h after modeling： model, cytoxan （CTX, 25 mg/kg） positive control, low-, mid-, and high-dose （20, 40, and 80 mg/kg） VOSAS groups. The mice were ip administered once daily for 10 d. Morphological changes in H22 solid tumor cells were observed by both Hematoxylin-eosin （HE） and acridine orange （AO） staining. The expression of Bax and Bcl-2 in the tumor tissue was determined using immunohistochemistry. Results VOSAS could inhibit the tumor growth and extend the life span of H22-bearing mice （P 〈 0.01）; and it could also raise the expression of Bax while suppress the expression of Bcl-2; the antitumor effect of VOSAS on H22-bearing mice demonstrated a good dose-effect relationship, but the high-dose group of the volatile oil has obvious toxicity and side effects on the mice. Conclusion VOSAS could inhibit the growth of H22 tumor cells and the mechanism may be related to up-regulating the expression of Bax and down-regulating the expression of Bcl-2, and the induction of apoptosis.