摘要
目的通过肺腺癌A549细胞裸鼠移植瘤模型实验,研究藏红花酸对肺腺癌放射敏感性的影响及可能机制。方法将40只构建的肺腺癌荷瘤小鼠随机分为对照组、藏红花酸组、放疗组、藏红花酸联合放疗组4组,给予相应的干预处理。14 d处理完成后处死所有小鼠并剥离肿瘤组织,测量每组肿瘤组织瘤重并计算抑瘤率;流式细胞术分析肿瘤细胞凋亡情况;免疫组化、RT-qPCR法检测移植瘤中缺氧诱导因子(HIF-1α)、B细胞淋巴瘤(BCL-2)基因的表达情况并比较。结果藏红花酸联合放疗组小鼠的平均瘤重明显低于单纯放疗组(P<0.05),抑瘤率为34.07%。与单纯放疗组相比,藏红花酸联合放疗组小鼠平均肿瘤细胞凋亡率明显升高(P<0.05)。藏红花酸联合放疗组的HIF-1α表达显著低于单纯放疗组(P=0.001)。藏红花酸联合放疗组BCL-2表达低于单纯放疗组,但差异无统计学意义(P=0.894)。藏红花酸联合放疗组的HIF-1αmRNA、BCL-2 mRNA表达均显著低于单纯放疗组(P<0.05)。结论联合使用藏红花酸显著增强了放射治疗对肺腺癌荷瘤小鼠肿瘤生长的抑制作用、提高了放射治疗的抑瘤率,可能是通过改善放射治疗造成的HIF-1α基因高表达状态进而改善放疗导致的肿瘤组织的缺氧状况和抑制抗凋亡基因BCL-2的表达进而增强了放疗导致的肺腺癌细胞凋亡这两种途径实现的。
Objective To investigate the effects of crocetin on radiosensitivity of lung adenocarcinoma and its potential mechanisms using a nude mouse xenograft model established with A549 lung adenocarcinoma cells.Methods Forty mice bearing lung adenocarcinoma were randomly divided into four groups:control group,crocetin group,radiotherapy group,and crocetin combined with radiotherapy group,and received the corresponding interventions.After 14 days of treatment,all mice were sacrificed and tumor tissues were excised.Tumor weight was measured in each group and the tumor inhibition rate was calculated.Apoptosis of tumor cells was analyzed by flow cytometry.Immunohistochemistry and RT-qPCR were used to detect and compare the expression of genes encoding hypoxia-inducible factor(HIF-1α)and B-cell lymphoma-2(BCL-2).Results The mean tumor weight of mice in the crocetin combined with radiotherapy group was significantly lower than that in the radiotherapy group(P<0.05),and the tumor inhibition rate of the crocetin combined with radiotherapy group was 34.07%.The mean tumor cell apoptosis rate in the crocetin combined with radiotherapy group was significantly higher than that in the radiotherapy group(P<0.05).HIF-1αexpression was significantly lower in the crocetin combined with radiotherapy group than in the radiotherapy group(P=0.001).Although BCL-2 expression in the crocetin combined with radiotherapy group was lower than that in the radiotherapy group,the difference was not statistically significant(P=0.894).The expression levels of mRNAs of genes encoding HIF-1αand BCL-2 in the crocetin combined with radiotherapy group were significantly lower than those in the radiotherapy group(P<0.05).Conclusion Crocetin in combination with radiotherapy significantly enhanced the inhibitory effect of radiotherapy on tumor growth in mice bearing lung adenocarcinoma and increased the tumor inhibition rate.The mechanisms may involve the alleviation of radiotherapy-induced overexpression of HIF-1α,thereby improving hypoxic conditions in tumor tissues,as well as suppression of the anti-apoptotic gene BCL-2 to enhance radiotherapy-induced apoptosis of lung adenocarcinoma cells.
作者
贺苗
张丽柯
马磊
徐全晓
HE Miao;ZHANG Like;MA Lei;XU Quanxiao(Xinxiang Medical College,Xinxiang 453003,China;Henan Provincial Key Laboratory of Cancer Molecular Biology and Medicine,The First People's Hospital of Nanyang City,Nanyang 473000,China)
出处
《中国辐射卫生》
2025年第4期523-529,共7页
Chinese Journal of Radiological Health
基金
苏州大学省部共建放射医学与辐射防护国家重点实验室开放研究课题(GZK1202120)。
