Cisplatin suppresses the growth and proliferation of breast and cervical cancer cell lines by inhibiting integrin β5-mediated glycolysis.
Cancer cells harbor lower energy consumption after rounds of anticancer drugs, but the underlying mechanism remains unclear. In this study, we investigated metabolic alterations in cancer cells exposed to cisplatin. The present study exhibited cisplatin, known as a chemotherapeutic agent interacting with DNA, also acted as an anti-metabolic agent. We found that glycolysis levels of breast and cervical cancer cells were reduced after cisplatin treatment, resulting in cells growth and proliferation inhibition. We demonstrated that cisplatin suppressed glycolysis-related proteins expression, including glucose transporter 1 (GLUT1), glucose transporter 4 (GLUT4) and lactate dehydrogenase B (LDHB), through down-regulating integrin β5 (ITGB5)/focal adhesion kinase (FAK) signaling pathway. ITGB5 overexpression rescued cisplatin-induced inhibition of cancer cell glycolysis, growth and proliferation. Conclusively, we reveal a novel insight into cisplatin-induced anticancer mechanism, suggesting alternative strategies to the current therapeutic approaches of targeting ITGB5, as well as of a combination of cisplatin with glucose up-regulation chemotherapeutic agents to enhance anticancer effect.
Cancer institute and Department of Gynecological Oncology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University270 Dong'an Road, Shanghai 200032, China.
Shaojia
S
Wang
Department of Medical Oncology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University270 Dong'an Road, Shanghai 200032, China.
Jie
J
Xie
Cancer institute and Department of Gynecological Oncology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University270 Dong'an Road, Shanghai 200032, China.
Jiajia
J
Li
Cancer institute and Department of Gynecological Oncology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University270 Dong'an Road, Shanghai 200032, China.
Fei
F
Liu
Cancer institute and Department of Gynecological Oncology, Fudan University Shanghai Cancer Center Shanghai 200032, China.
Xiaohua
X
Wu
Cancer institute and Department of Gynecological Oncology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Medical Oncology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University270 Dong'an Road, Shanghai 200032, China.
Ziliang
Z
Wang
Cisplatin; ITGB5; glucose metabolism; integrin