Autophagy suppresses bladder tumor formation in a mouse orthotopic bladder tumor formation model

  • 郭 琬婷

Student thesis: Master's Thesis


Autophagy is a catabolic process which involves in recruitment of unnecessary and damaged proteins and cellular components through degradation in the lysosomal machinery under stress conditions Autophagy plays a suppressive role in tumorigenesis through the degradation of oncoprotein Autophagy may be a potential therapy for cancer Therefore to find out a potential autophagy inducer drug as therapy route is needed X drug which is an antiarrhythmic drug was identified as an autophagy inducer Our in vitro study showed that X drug can induce autophagy and inhibit proliferation and colony formation of the MB49 mouse bladder cancer cells and the T24 human bladder cancer cells The mouse bladder cancer cell lines named MB49Luc stably expressing the luciferase gene were further established Orthotopic bladder tumor formation in C57BL/6 female mice after MB49Luc cell inoculation was further established and monitored by tracing bioluminescence expression under the IVIS imaging system Our results show that the bioluminescence expression accompanied with the tumor size of the treated mice was decreased after intravesical instillation of X drug We further confirm that bladder tumor was inhibited by hematoxylin and eosin stain X drug -induced autophagy in the bladder tissue of the treated mice was confirmed by immunohistochemistry and immunofluorescence assays X drug showed low side effect on the physiologic conditions of the treated mice Furthermore comparing the toxicity and efficacy of tumor suppression between X drug and clinical used anti-bladder cancer drug mitomycin C X drug and mitomycin C both show tumor suppression capability We also analyze the physiologic conditions of the treated mice Our results show that mitomycin C has significant side effect in the treated mice In summary intravesical delivery of X drug suppresses tumorigenesis of bladder cancer cells both in vitro and in vivo through activation of autophagy In the clinical therapeutic agents of bladder cancer patients we reveal that X drug is a novel off-labeling and low side effect agent
Date of Award2014 Aug 27
Original languageEnglish
SupervisorHsiao-Sheng Liu (Supervisor)

Cite this