大黄素、芹菜素抑制人卵巢癌细胞侵袭的体外实验研究

背景与目的:大黄素抑制酪氨酸蛋白激酶、酪蛋白激酶2的活性,抑制I-κB降解;芹菜素抑制丝裂原活化蛋白激酶、PI3K的活性。大黄素、芹菜素是否能抑制高恶性度肿瘤侵袭与转移的研究还未见报道,本研究选用大黄素、芹菜素,观察其对人卵巢癌细胞体外侵袭的作用。方法:台盼蓝活细胞拒染法观察药物对人卵巢癌细胞生长、增殖的影响;以人工重组基底膜(Matrigel)体外侵袭实验观察药物对细胞体外侵袭、粘附、运动能力的影响;SDS-聚丙烯酰胺凝胶电泳法观察对Ⅳ型胶原酶分泌及活性的影响。结果:大黄素及芹菜素均抑制HO-8910PM细胞的生长、增殖,其48h的IC50分别为(35.30±3.50)μmol/L和(28.92±2.60)μmol/L。大黄素有效抑制HO-8910PM细胞体外侵袭、粘附、运动,在40μmol/L时,抑制率分别为(45.31±3.10)%、(25.42±1.70)%和(41.59±1.90)%;大黄素抑制基质金属蛋白酶-9(MMP-9)分泌,但不能直接抑制其活性。芹菜素能抑制细胞粘附、运动,在40μmol/L时,抑制率分别为(30.80±3.00)%和(29.04±1.70)%,但抑制细胞体外侵袭作用不显著,仅为(12.08±0.50)%,且不能抑制MMP-9分泌也不能直接抑制其活性。结论:大黄素、芹菜素对人卵巢癌HO-8910PM细胞均有一定的毒性,而大黄素更具有成为抗肿瘤侵袭药物的潜力。

Effect of emodin and apigenin on invasion of human ovarian carcinoma HO-8910PM cells in vitro

BACKGROUND & OBJECTIVE: Emodin inhibited the activity of TPK and CK2 and the degradation of I-kappaB. Apigenin inhibited the activity of MAPK and PI(3)K. In this study the authors observed the effect of emodin and apigenin on the invasion of HO-8910PM cells in vitro. METHODS: Trypan blue dye exclusion assay was used to examine the cytotoxity of emodin and apigenin. Reconstituted basement membrane invasion assay was utilized to evaluate the invasive activity.Type IV collagenase production was analyzed by PAGE substrate zymography. RESULTS: Emodin had weaker cytotoxity on HO-8910PM cells than apigenin, their IC(50) after treatment with the chemicals for 48 hours were (35.30+/-3.50) micromol/L, and (28.92+/-2.60)micromol/L, while emodin significantly inhibited membrane invasion and adhesion and migration of HO-8910PM cells. Their inhibition rates after treated with the chemical of 40 micromol/L were (45.31+/-3.10)%,(25.42+/-1.70)%, and (41.59+/-1.90)%. Emodin inhibited the production but not activity of MMP-9. Apigenin inhibited migration and adhesion of HO-8910PM cells, their inhibition rates after treated with the chemical of 40 micromol/L were (29.04+/-1.70)% and (30.80+/-3.00)%, while weakly inhibited membrane invasion (the inhibition rate only was 12.1%) and inhibited neither production nor activity of MMP-9. CONCLUSION: Both emodin and apigenin had cytotoxicity on HO-8910PM cells. Emodin was a potential agent inhibiting tumor invasion and metastasis.