摘要
探讨西藏林芝桦褐孔菌提取物中的活性成分桦褐孔菌醇(inotodiol,INO)对肺癌的抗肿瘤作用及其可能机制。体外实验利用CCK-8、TUNEL染色、划痕实验和Transwell实验以及LC3染色分别检测INO干预人肺腺癌细胞系SPCA-1后的细胞活力,细胞凋亡,迁移和侵袭能力以及细胞内自噬水平的变化;体内实验利用SPCA-1细胞构建肺癌荷瘤鼠模型,成瘤后随机分组:模型组(model group,Mod)、阴性对照组(negative control,NC)、阳性对照组(positive control,PC)、INO低剂量组(low-dose INO,INO-L;50 mg/kg)、INO中剂量组(medium-dose INO,INO-M;100 mg/kg)、INO高剂量组(high-dose INO,INO-H;200 mg/kg)。每天检测荷瘤鼠体重及测量瘤体大小,灌胃给药20 d后处死荷瘤鼠,切除瘤体并称重,HE染色观察肿瘤组织病理变化。结果显示,体外实验中,与对照组(control,Con)相比,INO显著抑制SPCA-1细胞增殖(P<0.05)、迁移(P<0.001)和侵袭(P<0.01),促进SPCA-1细胞内自噬过量产生(P<0.05),从而诱导其凋亡(P<0.01);体内实验中,与Mod组相比,INO-L、INO-M和INO-H组瘤体重量和体积均显著下降(P<0.05,P<0.001);HE结果显示,INO-L、INO-M和INO-H组肿瘤组织内实质细胞密度降低,坏死细胞密度增加。但与Mod组相比,INO-L、INO-M和INO-H组荷瘤鼠体重无显著变化(P>0.05)。综上所述,INO具有良好的体内外抗肺癌活性,其机制可能与诱导细胞自噬和凋亡有关,且未见明显全身毒性,提示其有望作为潜在的新型抗肺癌候选药物。
This study aimed to investigated the antitumor effects and underlying mechanisms of inotodiol(INO),an active component of the extract of derived from Inonotus obliquus collected in Nyingchi,Xizang against lung cancer.A series of assays,including CCK-8,TUNEL staining,wound-healing assay,Transwell assay,as well as LC3 immunofluorescence staining,were performed to evaluate alterations in cell viability,apoptosis,migratory and invasive capabilities,and autophagy levels in the human lung adenocarcinoma cell line SPCA-1 following INO treatment in vitro.For in vivo studies,xenograft tumors were established in nude mice using SPCA-1 cells.After tumor formation,the mice were randomly assigned to six groups:model group(Mod),negative control group(NC),positive control group(PC),low-dose INO group(INO-L,50 mg/kg),middle-dose INO group(INO-M,100 mg/kg)and high-dose INO group(INO-H,200 mg/kg).The weight of the xenografted nude mice and the size of the tumor was measured daily.After 20 days of INO administration,the xenografted nude mice were euthanized,and the tumor tissues were excised,weighed,and subjected to histological analysis using HE staining.The results showed that compared with the control group,INO significantly inhibited the proliferation(P<0.05),migration(P<0.001),and invasion(P<0.01)of SPCA-1 cells.In vitro,while inducing excessive autophagy(P<0.05)and apoptosis(P<0.01)in vitro.In vivo,compared with Mod,the weight and volume of tumors in the INO-L,INO-M,and INO-H groups were significantly reduced(P<0.05,P<0.001);The HE results showed that the density of tumor cells decreased and the density of necrotic cells increased in the INO-L,INO-M,and INO-H groups.However,compared with Mod,there was no significant change in body weight in the INO-L,INO-M,and INO-H groups(P>0.05),indicating minimal systemic toxicity.In summary,INO exhibits potent anti-lung cancer activity both in vitro and in vivo,likely through the induction of autophagy and apoptosis,and demonstrates a favorable safety profile,indicating its potential as a new candidate drug for lung cancer therapeutics.
作者
李孟玲
张译丹
禄玉冰
严洁
元博
童晓鹏
薛蓓
LI Meng-ling;ZHANG Yi-dan;LU Yu-bing;YAN Jie;YUAN Bo;TONG Xiao-peng;XUE Bei(Key Laboratory of High Altitude Hypoxia Environment and Life Health,School of Medicine,Xizang Minzu University;Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Xizang Autonomous Region,School of Medicine,Xizang Minzu University,Xianyang 712082,China)
出处
《天然产物研究与开发》
北大核心
2025年第8期1433-1440,1410,共9页
Natural Product Research and Development
基金
西藏自治区科技计划(XZ201801-GA-15)
国家自然科学基金地区项目(82460849)
西藏民族大学科研启动费(24XZMDQD01)。
