Basic and clinical Research for Caveolin as a therapeutic target for urogenital cancer

Caveolin作为泌尿生殖系统癌症治疗靶点的基础和临床研究

• 批准号: 13671652
• 负责人: NASU Yasutomo
• 金额: $ 2.24万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671652/
• 关键词: Caveolin; androgen; baladder cancer; prostate cancer; MDR; MRP

Purpose of this research is to elucidate the basic and clinical implication. of caveolin as a therapeutic molecular target for urogenital cancer. We have highlighted the mechanistic analysis of the formation of multi drug resistance for anti-cancer drugs. Expression study of caveolin, multidrug resistance related molecules (MDR, MRP) was performed using cultured cells and clinical samples. Caveolin expression was also analyzed morphologically using transmission electron microscope as a form of caveolae.1)Bladder cancer cell linesParent and induced Adriamycin (ADM) resistant bladder cell lines (T-24 vs T-24/ADM and KK-47 vs KK-47/ADM) were analyzed. Caveolin expression decreased in T-24/ADM compared to T-24 but increased in KK-47/ADM compared to KK-47. Expression level of caveolin protein positively correlated with the number of caveolae detected by TEM. MDR was positive in KK-47/AD. MRP was positive in T-24/ADM and KK-47/ADM. Expression of MDR was positively correlated with caveolin in the process of drug resistance formation.2)Clinical sample of bladder cancerClinical samples were obtained from the patients who showed resistance or recurrence to conventional anticancer drug treatment including ADM. No correlation was observed among the protein expression of caveolin, MDR and MRP3)Prostate cancer cell linesHuman prostate cancer cell lines (PC-3, DU-145, LNCap) were analyzed with the same methods used in the analysis of the bladder cancer, No correlation was observed among the protein expression of cave olin, MDR and MRP

本研究的目的是阐明其基础和临床意义。caveolin作为泌尿生殖系统癌症的治疗分子靶点。我们重点分析了抗癌药物多药耐药形成的机制。用培养细胞和临床标本研究窖蛋白、多药耐药相关分子（MDR、MRP）的表达。1）膀胱癌细胞系分析亲本和诱导的阿霉素（ADM）耐药膀胱细胞系（T-24 vs T-24/ADM和KK-47 vs KK-47/ADM）。与T-24相比，T-24/ADM中小窝蛋白表达降低，但与KK-47相比，KK-47/ADM中小窝蛋白表达增加。小窝蛋白的表达水平与透射电镜观察到的小窝数目呈正相关。KK-47/AD多药耐药阳性。MDR在T-24/ADM和KK-47/ADM中呈阳性表达，在耐药形成过程中MDR的表达与caveolin呈正相关。2）膀胱癌临床标本临床标本取自对包括ADM在内的常规抗癌药物治疗耐药或复发的患者。MDR和MRP 3）前列腺癌细胞系采用与膀胱癌相同的方法分析人前列腺癌细胞系（PC-3、DU-145、LNCap），未观察到cave olin、MDR和MRP蛋白表达之间的相关性

项目成果

Ebara S: "Gene therapy for prostate cancer : toxicological profile of four HSV-tk transducing adenoviral vectors regulated by different promoters."Prostate Cancer Prostatic Dis. 5(4). 316-325 (2002)

Ebara S：“前列腺癌的基因治疗：四种由不同启动子调控的 HSV-tk 转导腺病毒载体的毒理学特征。”前列腺癌前列腺疾病。

Kraaji R.: "Validation of transrectal ultrasonographic volumetry for orthotopic prostate tumours in mice"Lab Anim. 36(2). 165-172 (2002)

Kraaji R.：“小鼠原位前列腺肿瘤经直肠超声容量测定的验证”实验室动画。

那須保友, 公文裕巳: "前立腺癌遺伝子治療の現状と展望"岡山医学会雑誌. 114. 173-177 (2002)

Yasutomo Nasu、Hiromi Kumon：“前列腺癌基因治疗的现状和前景”冈山医学会杂志 114. 173-177 (2002)。

Y, Nasu: "Androgen dependency and caveolin"Urological Review. 3. 2-5 (2001)

Y，Nasu：“雄激素依赖性和小窝蛋白”泌尿外科评论。

那須保友: "前立腺癌のアンドロゲン依存性とカベオリン"Urological Review. 3(3). 2-5 (2001)

Yasutomo Nasu：“前列腺癌中的雄激素依赖性和小窝蛋白”泌尿学评论 3(3) (2001)。