<p>Metformin Combined with 4SC-202 Inhibited the Migration and Invasion of OSCC via STAT3/TWIST1</p>

Abstract

Background Oral squamous cell carcinoma (OSCC), the most common epithelial malignant neoplasm in the head and neck, characterizes with local infiltration and metastasis of lymph nodes. The five-year survival rate of OSCC remains low despite the advances in clinical methods. Thus, it is necessary to develop a new effective therapeutic scheme for OSCC. Our previous results showed that metformin and 4SC-202 synergistically promoted the intrinsic apoptosis of OSCC in vitro and in vivo, but the effects on invasion and migration remained unclear. Methods Human OSCC cell lines HSC6 and CAL33 were cultured with metformin (16 mM) or/and 4SC-202 (0.4 μM) for 72 h. STAT3 inhibitor S31-201 was applied at concentration of 60 μM for 48 h. Wound-healing assays and transwell assays were used to determine the invasion and migration ability of OSCC. qRT-PCR and Western blot were performed to detect mRNA levels and protein levels. Results Metformin or/and 4SC-202 suppressed the migration and invasion of OSCC cells. Importantly, the expression of TWIST1 was suppressed by metformin and 4SC-202, while the invasion and migration inhibitory effects of metformin and 4SC-202 were countered by the overexpression of TWIST1. In addition, the phosphorylation level of STAT3 decreased after the administration of metformin or/and 4SC-202. Furthermore, inhibition of STAT3 by S31-201 suppressed the expression of TWIST1 and led to a decline in migration and invasion of OSCC, while overexpression of TWIST1 attenuated these effects. Conclusion Metformin and 4SC-202 suppressed the invasion and migration of OSCC through inhibition of STAT3/TWIST1, and this scheme can serve as a novel therapeutic strategy for OSCC.

METTL3 Intensifies the Progress of Oral Squamous Cell Carcinoma via Modulating the m6A Amount of PRMT5 and PD-L1

“…Oral squamous cell carcinoma (OSCC) is the commonest head and neck malignancy and responsible for approximately 90% of malignant epithelial tumors in the oral and maxillofacial region [1][2][3][4]. Over the years, comprehensive treatments, which include radiotherapy, chemotherapy, and surgical treatment, have made progress, but poor prognosis remains in OSCC patients, and the 5-year survival rate is roughly 60 [5][6][7][8][9].…”

Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment

“…More specifically, this study evaluated the effects of metformin, 4SC-202, a novel selective class I histone deacetylase inhibitor (HDACi) that has previously been reported to inhibit the survival and proliferation of several types of cancer cells including OCSCC, or their combination. Metformin combined with 4SC-202 blunted OSCC cell migration and invasion by suppressing STAT3/TWIST1 signaling [ 41 ]. This study is of paramount importance.…”

Inflammation and Invasion in Oral Squamous Cell Carcinoma Cells Exposed to Electronic Cigarette Vapor Extract

“…We first investigated expression of NF-kB, ERK and JNK in Ca9 To further characterized EVE effects on OSCC, we investigated its effect on cell invasion. OSCC is characterized by high incidence of local invasion and metastasis that leads to poor prognosis (21). This invasiveness is known to be regulated 4B, C).…”