目的 研究蝎毒多肽抑制卵巢癌裸鼠肿瘤生长的作用机制, 为恶性肿瘤临床治疗提供理论依据。方法 制备人SKOV3裸鼠异种移植瘤模型, 蝎毒多肽高、低剂量(20、10 mg/kg)ig给药2周, 绘制肿瘤体积增长曲线, 并计算抑瘤率;HE染色法观察各组肿瘤组织病理变化;免疫组化法检测肿瘤组织中PTEN、PI3K、p-Akt的表达水平;ELISA法检测各组裸鼠血清中PTEN、PI3K、p-Akt水平。结果 蝎毒多肽高、低剂量组的抑瘤率分别为50.8%和31.5%。与对照组相比, 蝎毒多肽高、低剂量组裸鼠肿瘤组织中PI3K和p-Akt的表达明显下调(P<0.05、0.01), PTEN的表达明显上调(P<0.05、0.01);血清中各因子的变化与免疫组化结果一致。结论 蝎毒多肽可抑制卵巢癌肿瘤的生长, 其机制可能与抑制肿瘤微环境中PI3K、p-Akt的表达, 上调PTEN的表达有关。

Objective To research the inhibitory mechanism of the polypeptide extract from scorpion venom (polypeptide extract from scorpion venom, PESV) on tumor growth, which would provides the theory basis for clinic treatment of malignant tumor. Methods SKOV3 xenograft models were established, and tumors were excised after administration to observe the inhibitory effect of PESV. The effect of PESV on the tumor growth was observed by recording tumor growth curve and calculating the inhibitory rate; Immunohistochemistry and ELISA were applied to detect the levels of PTEN, PI3K, and P-Akt. Results The inhibitory rates of the high-dose (20 mg/kg) and low-dose (10 mg/kg) PESV groups were 50.8% and 31.5%. Compared with the control group, the protein expressions of PI3K and P-Akt significantly decreased (P < 0.05 or 0.01) and the protein expressions of PTEN significantly increased (P < 0.05 or 0.01) in the high-and low-dose PESV groups. Conclusion PESV could inhibit the growth of ovarian cancer. Its mechanisms might be associated with inhibiting the expressions of PI3K and P-Akt and increasing PTEN in the microenvironment of tumors.

国家自然科学基金资助项目(81073102, 30873408)