Combined Inhibition of PI3K and STAT3 signaling effectively inhibits bladder cancer growth.

Peng, Weidong; Zhang, Haojie; Yin, Mingwei; Kong, Dejie; Kang, Liping; Teng, Xinkun; Wang, Jingjing; Chu, Zhimin; Sun, Yating; Long, Pengpeng; Cui, Chengying; Lyu, Bin; Zhang, Jinzhi; Xiao, Han; Wu, Mingqing; Wang, Yongqiang; Li, Yang

Peng, Weidong; Zhang, Haojie; Yin, Mingwei; Kong, Dejie; Kang, Liping; Teng, Xinkun; Wang, Jingjing; Chu, Zhimin; Sun, Yating; Long, Pengpeng; Cui, Chengying; Lyu, Bin; Zhang, Jinzhi; Xiao, Han; Wu, Mingqing; Wang, Yongqiang; Li, Yang.

Afiliación

Peng W; Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China.
Zhang H; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Yin M; Department of Urology, Huadong Hospital, Fudan University, Shanghai, China.
Kong D; Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Kang L; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Teng X; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Wang J; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Chu Z; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Sun Y; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Long P; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Cui C; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Lyu B; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Zhang J; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Xiao H; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China.
Wu M; Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Wang Y; Department of Genetics, School of Life Science, Anhui Medical University, Hefei, China. wumingqing93@163.com.
Li Y; Department of Urology, South China Hospital, Medical School, Shenzhen University, Shenzhen, China. wangyongqiang@szu.edu.cn.

Oncogenesis ; 13(1): 29, 2024 Jul 27.

Article en En | MEDLINE | ID: mdl-39068158

ABSTRACT

ABSTRACT

Bladder cancer is characterized by aberrant activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling, underscoring the significance of directing therapeutic efforts toward the PI3K pathway as a promising strategy. In this study, we discovered that PI3K serves as a potent therapeutic target for bladder cancer through a high-throughput screening of inhibitory molecules. The PI3K inhibitor demonstrated a robust anti-tumor efficacy, validated both in vitro and in vivo settings. Nevertheless, the feedback activation of JAK1-STAT3 signaling reinstated cell and organoid survival, leading to resistance against the PI3K inhibitor. Mechanistically, the PI3K inhibitor suppresses PTPN11 expression, a negative regulator of the JAK-STAT pathway, thereby activating STAT3. Conversely, restoration of PTPN11 enhances the sensitivity of cancer cells to the PI3K inhibitor. Simultaneous inhibition of both PI3K and STAT3 with small-molecule inhibitors resulted in sustained tumor regression in patient-derived bladder cancer xenografts. These findings advocate for a combinational therapeutic approach targeting both PI3K and STAT3 pathways to achieve enduring cancer eradication in vitro and in vivo, underscoring their promising therapeutic efficacy for treating bladder cancer.

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncogenesis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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