莪术油对卵巢癌裸鼠移植瘤的抑制作用及其联合顺铂的协同作用研究

Antitumor Effect and Synergistic Effect with Cisplatin of Zedoray Turmeric Oil on Nude Mice Bearing Ovarian Cancer

关键词:  莪术油  卵巢癌  抗肿瘤作用  顺铂  协同治疗

Key words:  zedoray turmeric oil  ovarian cancer  antitumor effect  cisplatin  synergistic treatment

摘要:

目的 探讨莪术油对卵巢癌裸鼠移植瘤的抑制作用，并探讨其与顺铂联合的协同作用。方法 建立卵巢癌细胞株HO-8910PM荷瘤裸鼠模型，随机分为模型对照组、莪术油组、顺铂组和联合给药组（莪术油+顺铂）4组，每组6只，分别腹腔注射莪术油（300 mg·kg^-1）、顺铂（2 mg·kg^-1）、莪术油联合顺铂（300 mg·kg^-1+2 mg·kg^-1）以及空白对照液（0.4 mL生理盐水），给药3周后处死小鼠并测瘤体积变化，计算肿瘤生长抑制率，免疫组化检测各组肿瘤组织中NM23、TNF-α、VEGF、NF-KBP65、PCNA的蛋白表达。ELISA检测裸鼠血清中IL-2、IFN-γ水平。结果 与模型对照组比较，莪术油、顺铂及其联合给药后均能显著抑制裸鼠肿瘤体积的增长（P<0.05或P<0.01），且联合给药的抑瘤率（55.06%）要高于莪术油（20.5%）和顺铂（52.52%）单独给药。免疫组化检测结果显示各组药物治疗后，能显著降低裸鼠肿瘤组织中NM23、TNF-α、VEGF、NF-KBP65、PCNA的阳性表达（P<0.05或P<0.01），且降低程度从低到高依次为莪术油组、顺铂组、联合给药组。ELISA检测结果也表明顺铂以及莪术油联合顺铂给药3周后能显著提高裸鼠血清IL-2、IFN-γ水平（P<0.01），且含量上升程度由低到高依次为莪术油组、顺铂组、联合给药组。结论 莪术油能够抑制卵巢癌荷瘤裸鼠移植瘤的增长，具有一定的抗肿瘤效果，其机制可能与调节肿瘤生长因子NM23、TNF-α、VEGF、NF-KBP65、PCNA及免疫相关因子IL-2、IFN-γ的表达有关。莪术油联合顺铂用药对卵巢癌肿瘤的抑制具有潜在的协同作用，但还需更深入实验研究。

Abstract:

OBJECTIVE To investigate antitumor effect of zedoray turmeric oil(ZTO) on nude mice bearing ovarian cancer and explore its synergistic effect with cisplatin. METHODS After the establishment of HO-8910PM tumor-bearing mice model, the mice were randomly divided into four groups:model control group(normal saline); ZTO group (300 mg·kg^-1); cisplatin group (2 mg·kg^-1); combination group(300 mg·kg^-1 ZTO+2 mg·kg^-1 cisplatin). The nude mice were sacrificed after three weeks of treatment, tumor volume in each group were detected and tumor inhibition rate were calculated. The expression of NM23, TNF-α, VEGF, NF-KBP65, PCNA in tumor tissues were determined by immunohistochemical. ELISA analysis was performed to evaluate the serum level of IL-2 and IFN-γon in nude mice. RESULTS Compared with model group, the tumor volume were significantly decreased in ZTO, cisplatin and combination group(P<0.05 or P<0.01). And the tumor inhibition rates were 20.55%, 52.52%, 55.06%, respectively. Immunohistochemical results showed that the expression of NM23, TNF-α, VEGF, NF-KBP65, PCNA could be significantly decreased with the administration of ZTO, cisplatin, ZTO and cisplatin combined (P<0.05 or P<0.01), and the tendency from low to high were ZTO, cisplatin, ZTO and cisplatin combined in turn. The levels of IL-2 and IFN-γ were also significantly increased with treatment of cisplatin as well as ZTO and cisplatin combined (P<0.01), and the tendency from low to high was the same to above. CONCLUSION ZTO has the anti-tumor effect on ovarian cancer, the underlying mechanism maybe related with regulation of the expression of tumor growth cytokine NM23, TNF-α, VEGF, NF-KBP65, PCNA and immune-related factors IL-2, IFN-γ. And ZTO combined with cisplatin have potential synergistic attenuated the antitumor effect in nude mice of ovarian cancer.