普奈洛尔对胃癌放疗敏感性影响及其机制的实验研究

Effects of propranolol in combination with radiation in gastric cancer: An experimental study

目的:从体内实验探究普萘洛尔对胃癌放疗敏感性的作用。方法:使用胃癌细胞株SGC-7901和BALA/C-nunu裸鼠皮下移植瘤模型,利用β受体阻滞剂干预裸鼠,通过测量胃癌移植瘤重量和体积判断肿瘤生长情况,通过免疫组织化学法和Western blot法研究NF-κB、EGFR、COX-2和VEGF的表达。结果:在裸鼠体内实验发现,在放疗前给予普奈洛尔可以明显减小移植瘤的体积及重量,起到抑制肿瘤生长和促进肿瘤凋亡的作用。通过免疫组织化学染色和Western blot发现放疗前使用普奈洛尔较单独使用放射治疗,可以降低细胞及组织NF-κB表达,并下调其下游相关分子VEGF、EGFR和COX-2的表达,从而抑制胃癌细胞的增殖及抑制其侵袭转移的能力。而在单独使用相同剂量普奈洛尔进行干预未见上述变化。结论:通过β受体阻滞剂普奈洛尔可以加强细胞和组织对放射治疗的敏感性,从而阻断NF-κB表达,下调核转录因子下游相关分子VEGF、EGFR和COX-2的表达,抑制胃癌细胞的增殖及抑制其侵袭转移的能力。提示β受体阻滞剂可作为胃癌的放疗增敏剂,有抗增殖、促凋亡、抑制侵袭和转移能力,为提高胃癌放疗效果提供基础,为探索新的放疗增敏剂提供理论依据。

Objective To evaluate if propranolol could enhance radiosensitivity and explore its precise molecular mechanism in gastric cancer in vivo study. Methods： Human gastric adenocarcinoma cell lines （SGC-7901） were cultured for research.Tumor models were created by nude mice and then treated with propranolol or/and radiation.Then,the data of tumor weight and volume were obtained for the statistical analysis.Moreover,the expression of NF-κB,EGFR,COX-2 and VEGF were detected by Western blot and immunohistochemical stain. Results： In nude mice,it was found that giving propranolol before radiotherapy can significantly reduce the volume and weight of transplanted tumor,inhibit tumor growth and promote tumor apoptosis.Immunohistochemical staining and Western blot found that the use of propranolol before radiotherapy compared with radiotherapy can reduce the cell and tissue NF-κB expression and down-regulate expression of VEGF,EGFR and COX-2 genes,thereby inhibiting gastric cancer cell proliferation and inhibiting the ability of invasion and metastasis. Conclusion： These results suggested that propranolol enhanced the sensitivity of gastric cancer to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway.