黄芩苷介导光动力疗法治疗宫颈癌的疗效及其机制研究

Study on Therapeutic Effects and Mechanism of Baicalin-mediated Photodynamic Therapy for Cervical Cancer

目的:观察黄芩苷介导光动力疗法(PDT)治疗宫颈癌的疗效,探讨其可能机制。方法:将宫颈癌Hela细胞悬液注入裸鼠皮下,构建移植瘤模型,成模后随机均匀分为模型组、黄芩苷-PDT观察组、PDT观察组、姜黄素-PDT观察组4组,每组18只。PDT观察组:肿瘤周围注射100μL生理盐水,6 h后瘤周注射硼砂缓冲液100μL后行PDT治疗,照射剂量为80 J/cm 2(435 nm波长,0.60 A,0.54 W,距离肿瘤表面3~5 cm,照射2 min 28 s);黄芩苷-PDT观察组:以80μg/mL的黄芩苷溶液100μL代替生理盐水,其他同PDT观察组;姜黄素-PDT观察组:以50μmol/L的姜黄素溶液100μL代替生理盐水,其他同PDT观察组;模型组:以自然光照代替PDT治疗,其他同PDT观察组。治疗1 d后,各组处死6只取材肿瘤组织制备成病理切片,HE染色观察组织病理学改变;另外处死6只,利用蛋白质印迹法检测肿瘤组织中Bcl-2和Bax蛋白的表达情况;剩余6只分别于治疗第1、3、7、14 d测量肿瘤体积,计算肿瘤体积抑瘤率。结果:模型组肿瘤体积持续增大,光动力治疗1 d后肿瘤组织出现坏死,肿瘤生长受到抑制,黄芩苷-PDT观察组和姜黄素-PDT观察组肿瘤体积在3 d内均无增大趋势,随后逐渐增大。黄芩苷-PDT观察组Bcl-2和Bax蛋白表达与模型组比较,差异有统计学意义(P<0.05)。结论:黄芩苷介导的PDT能够有效抑制宫颈癌体外移植瘤的增长,其机制可能通过促进癌细胞凋亡发挥作用。

Objective:To observe the therapeutic effects of baicalin-mediated photodynamic therapy(PDT)on cervical cancer and explore its possible mechanism.Methods:A cervical cancer Hela cell suspension was injected subcutaneously into nude mice to construct a transplanted tumor model.After the model was formed,it was randomly and evenly divided into 4 groups:a model group,a baicalin-PDT treatment group,a PDT treatment group,and a curcumin-PDT treatment group,with 18 cases in each group.PDT treatment group:100μL of saline was injected around the tumor,and 100μL of borax buffer was injected around the tumor 6 hours later,followed by PDT treatment.The irradiation dose was 80J/cm2(435nm wavelength,0.60A,0.54W,3-5cm from the tumor surface,irradiation 2 min28s);Baicalin-PDT treatment group:100μL of baicalin solution at 80μg/mL instead of normal saline,others were the same as PDT treatment group;curcumin-PDT treatment group:50μmol/L curcumin solution instead of 100 ml normal saline,others were the same as PDT treatment group;model group:natural light instead of PDT treatment,others were the same as PDT treatment group.After 1 day of treatment,6 rats were sacrificed in each group and their tumor tissues were prepared for pathological sections,and the histopathological changes were observed by HE staining;another 6 were sacrificed,and the expression of Bcl-2 and Bax proteins in tumor tissues were detected by Western blot technology;their tumor volume of 6 remaining rats,was measured only on the 1st,3rd,7th,and 14th days of treatment,and the tumor volume inhibition rate was also calculated.Results:The tumor volume in the model group continued to increase.Tumor tissue appeared necrosis and tumor growth was inhibited after 1 day of photodynamic therapy.The tumor volume of baicalin-PDT treatment group and curcumin-PDT treatment group did not increase within 3 days,and then gradually increased.The expression of Bcl-2 and Bax proteins in the baicalin-PDT treatment group was significantly different from that in the model group(P<0.01).Conclusion:Baicalin-mediated PDT can effectively inhibit the growth of cervical cancer xenografts in vitro,and its mechanism may play a role in promoting cancer cell apoptosis.