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ABSTRACT: Background
This study is to investigate the effects of zoledronic acid (ZA) on TSC2-null cell proliferation and on the tumor progression and recurrence in mouse models of lymphangioleiomyomatosis (LAM).Methods
Subcutaneous mouse models and LAM mouse models were established. Immunohistochemistry and immunofluorescence were performed to detect the protein expression levels. TUNEL assay was conducted to detect cell apoptosis. Immunoprecipitation was carried out to determine the interaction between proteins.Results
ZA prevented the growth of TSC2-null cells both in culture and in LAM mouse models. Compared with rapamycin, ZA more effectively promoted the apoptosis of TSC2-null cells. Moreover, combined with the rapamycin, ZA effectively suppressed the tumor recurrence after drug withdrawal and ZA inhibited the activity of GTPase RhoA by decreasing protein geranylgeranylation, resulting in changes of Yap nucleus translocation.Conclusion
ZA promotes cell apoptosis in TSC2-null cells through the RhoA/YAP signaling pathway. ZA may be used for the clinical treatment of LAM.
SUBMITTER: Zhao D
PROVIDER: S-EPMC7011352 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Zhao Dandan D Wu Jing J Zhao Yinjuan Y Shao Wei W Cheng Qi Q Shao Xiaoyan X Yuan Xianwen X Ye Juan J Gao Jianpu J Jin Meiling M Li Chaojun C Chen Xiaolin X Zhao Yue Y Xue Bin B
Cancer cell international 20200210
<h4>Background</h4>This study is to investigate the effects of zoledronic acid (ZA) on TSC2-null cell proliferation and on the tumor progression and recurrence in mouse models of lymphangioleiomyomatosis (LAM).<h4>Methods</h4>Subcutaneous mouse models and LAM mouse models were established. Immunohistochemistry and immunofluorescence were performed to detect the protein expression levels. TUNEL assay was conducted to detect cell apoptosis. Immunoprecipitation was carried out to determine the inte ...[more]