Published online Aug 15, 2021. doi: 10.4251/wjgo.v13.i8.893
Peer-review started: May 20, 2021
First decision: June 12, 2021
Revised: June 17, 2021
Accepted: July 5, 2021
Article in press: July 5, 2021
Published online: August 15, 2021
Processing time: 86 Days and 2.6 Hours
Esophageal squamous cell carcinoma (ESCC) is one of the most common ma
To investigate the antitumor effect of DHTS in ESCC and the underlying mecha
CCK-8 assay and cell cycle analysis were used to detect proliferation and cell cycle in ESCC cells. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining were used to detect apoptosis in ESCC cells. Western blot was used to detect the expression of proteins associated with the mitochondrial pathway. Immunofluorescence was used to detect the expression of phosphorylated STAT3 (pSTAT3) in DHTS-treated ESCC cells. ESCC cells with STAT3 knockdown and overexpression were constructed to verify the role of STAT3 in DHTS induced apoptosis. A xenograft tumor model in nude mice was used to evaluate the antitumor effect of DHTS in vivo.
After treatment with DHTS, the proliferation of ESCC cells was inhibited in a dose- and time-dependent manner. Moreover, DHTS induced cell cycle arrest in the G0/1 phase. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining revealed that DHTS induced obvious apoptosis in KYSE30 and Eca109 cells. At the molecular level, DHTS treatment reduced the expression of pSTAT3 and anti-apoptotic proteins, while increasing the expression of pro-apoptotic proteins in ESCC cells. STAT3 knockdown in ESCC cells markedly promoted the activation of the mitochondrial pathway while STAT3 overexpression blocked the activation of the mitochondrial pathway. Additionally, DHTS inhibited tumor cell proliferation and induced apoptosis in a xenograft tumor mouse model.
DHTS exerts antitumor effect in ESCC via STAT3-mediated activation of the mitochondrial pathway. DHTS may be a novel therapeutic agent for ESCC.
Core Tip: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with a poor prognosis. Our research found that dihydrotanshinone I (DHTS) suppresses proliferation and induces apoptosis in ESCC cells. Besides, STAT3-mediated activation of the mitochondrial pathway plays a vital role in DHTS-induced apoptosis. DHTS may be a promising candidate for the treatment of ESCC.