TY - JOUR
T1 - AMTB, a TRPM8 antagonist, suppresses growth and metastasis of osteosarcoma through repressing the TGFβ signaling pathway
AU - Liu, Yujie
AU - Leng, Ao
AU - Li, Lin
AU - Yang, Bo
AU - Shen, Shihui
AU - Chen, Hui
AU - Zhu, Enhao
AU - Xu, Qiyue
AU - Ma, Xiaoyu
AU - Shi, Peilin
AU - Liu, Yun
AU - Liu, Tielong
AU - Li, Lei
AU - Li, Kun
AU - Zhang, Dan
AU - Xiao, Jianru
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/3
Y1 - 2022/3
N2 - Since its first identification in prostate cancers and prostate tissues, transient receptor potential melastatin-subfamily member 8 (TRPM8) is subsequently found to be overexpressed in a wide range of cancers and is shown to be implicated in tumorigenesis and tumor progression. Here, we used N-(3-aminopropyl)-2-[(3-methylphenyl) methoxy] -N-(2-thienylmethyl) benzamide hydrochloride (AMTB), a specific TRPM8 antagonist, to explore its antitumoral effect on osteosarcoma. We find that AMTB suppresses osteosarcoma cell proliferation, metastasis and induces cellular apoptosis. Xenograft model in nude mice experiments also define that AMTB can increase the sensitivity of tumor cells to cisplatin, the cytotoxic chemotherapeutic regimens in treating osteosarcoma. Molecularly, AMTB specifically antagonizes TRPM8 which is upregulated in osteosarcoma and its expression level in osteosarcoma tissues is negatively related to patients’ prognosis. Finally, RNA sequencing analysis was performed to explore the mechanism underlying the antitumoral effect of AMTB on osteosarcoma cells and the results prove that AMTB suppresses the Transforming Growth Factor β (TGFβ) signaling pathway. Our study provides evidence that TRPM8 could be a potential therapeutic target and AMTB can suppress growth and metastasis of osteosarcoma cells through repressing the TGFβ signaling pathway and increase the sensitivity of tumor cells to cisplatin.
AB - Since its first identification in prostate cancers and prostate tissues, transient receptor potential melastatin-subfamily member 8 (TRPM8) is subsequently found to be overexpressed in a wide range of cancers and is shown to be implicated in tumorigenesis and tumor progression. Here, we used N-(3-aminopropyl)-2-[(3-methylphenyl) methoxy] -N-(2-thienylmethyl) benzamide hydrochloride (AMTB), a specific TRPM8 antagonist, to explore its antitumoral effect on osteosarcoma. We find that AMTB suppresses osteosarcoma cell proliferation, metastasis and induces cellular apoptosis. Xenograft model in nude mice experiments also define that AMTB can increase the sensitivity of tumor cells to cisplatin, the cytotoxic chemotherapeutic regimens in treating osteosarcoma. Molecularly, AMTB specifically antagonizes TRPM8 which is upregulated in osteosarcoma and its expression level in osteosarcoma tissues is negatively related to patients’ prognosis. Finally, RNA sequencing analysis was performed to explore the mechanism underlying the antitumoral effect of AMTB on osteosarcoma cells and the results prove that AMTB suppresses the Transforming Growth Factor β (TGFβ) signaling pathway. Our study provides evidence that TRPM8 could be a potential therapeutic target and AMTB can suppress growth and metastasis of osteosarcoma cells through repressing the TGFβ signaling pathway and increase the sensitivity of tumor cells to cisplatin.
UR - https://www.scopus.com/pages/publications/85127435306
U2 - 10.1038/s41419-022-04744-6
DO - 10.1038/s41419-022-04744-6
M3 - 文章
C2 - 35361751
AN - SCOPUS:85127435306
SN - 2041-4889
VL - 13
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 3
M1 - 288
ER -
