Repurposing homoharringtonine for thyroid cancer treatment through TIMP1/FAK/PI3K/AKT signaling pathway
Chuang Xi,
Guoqiang Zhang,
Nan Sun,
Mengyue Liu,
Nianting Ju,
Chentian Shen,
Hongjun Song,
Quanyong Luo,
Zhongling Qiu
Affiliations
Chuang Xi
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Guoqiang Zhang
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Nan Sun
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Mengyue Liu
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Nianting Ju
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Chentian Shen
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Hongjun Song
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Quanyong Luo
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Corresponding author
Zhongling Qiu
Department of Nuclear Medicine, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China; Corresponding author
Summary: Homoharringtonine (HHT), an alkaloid isolated from Cephalotaxus, is an effective anti-leukemia agent and exhibits inhibitory effects in various solid tumors. However, the impacts of HHT treatment on thyroid cancer (TC) remain unclear. Our findings demonstrated that HHT exhibited remarkable anti-TC activity that involved inhibiting cell proliferation, invasion, and migration, as well as inducing apoptosis. Proteomics analysis revealed that the expression of the tissue inhibitor of metalloproteinase 1 (TIMP1) was downregulated in TC cells after HHT treatment. TIMP1 overexpression promoted TC progression and partially reversed the anti-TC effects of HHT, while TIMP1 downregulation inhibited TC progression and enhanced the anti-TC effects of HHT. Furthermore, TIMP1 re-expression attenuated the enhancement of anti-TC effects of HHT induced by TIMP1 knockdown. Mechanistically, HHT exerted anti-TC effects by downregulating TIMP1 expression and then inactivating the FAK/PI3K/AKT signaling pathway. Taken together, our study demonstrated that HHT could inhibit TC progression by inhibiting the TIMP1/FAK/PI3K/AKT signaling pathway.
