Bupivacaine Inhibits the Malignant Biological Behavior of Oral Squamous Cell Carcinoma Cells by Inhibiting the Activation of ERK1/2 and STAT3

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2021 Jun 24

PMID 34164473

Citations 2

Authors

Zhongchao Wang

Jie Zhang

Yongmei Wen

Pin Wang

Liyuan Fan

Affiliations

Soon will be listed here.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is an aggressive malignant tumor. Bupivacaine (Bupi), a local anesthetic drug, has been shown to display anti-tumor activity against a variety of tumors.

Methods: We selected OSCC CAL-27 cells as the model. Cell toxicity, proliferation, apoptosis, and stemness were conducted, respectively. The protein levels of Ki67, PCNA, caspase-3, caspase-9, survivin, SOX2, NANOG, OCT4, STAT3, p-STAT3, ERK1/2, and p-ERK1/2 were evaluated by western blotting. Male BALB/c nude mice xenograft model was used to evaluate the effect of Bupi on tumor growth .

Results: Compared with the control group, Bupi (0.2, 0.5, or 1 µm) significantly decreased the cell viability and the proliferation of CAL-27 cells. Meanwhile, Bupi significantly promoted apoptosis of CAL-27 cells compared with the control group. Additionally, Bupi inhibited the stemness of CAL-27 cells which was evidenced by a sphere formation assay. Bupi decreased the phosphorylation level of STAT3 and ERK1/2 in a dose-dependent manner. The addition of interferon-γ (IFN-γ, 20 ng/mL) in the experiment verified the role of Bupi on STAT3 and ERK1/2 signaling. , Bupi (40 µmol/kg) obviously suppressed the weight and size of the xenograft tumor, the number of apoptotic cells and Ki67+ decreased. Also, Bupi treatment inhibited the expression of stem-like marker proteins.

Conclusions: Bupi could be used as an anticancer drug against the growth and stemness ability of OSCC. The underlying mechanism may be due to down-regulation of STAT3 and ERK1/2 signaling. This study provides a new insight for the application of Bupi.

Citing Articles

Long-Term Outcomes of Breast Cancer Patients Receiving Levobupivacaine Wound Infiltration or Diclofenac for Postoperative Pain Relief.

Glavas Tahtler J, Djapic D, Neferanovic M, Miletic J, Milosevic M, Kralik K Pharmaceutics. 2023; 15(9).

PMID: 37765154 PMC: 10534840. DOI: 10.3390/pharmaceutics15092183.

STAT3 and Its Targeting Inhibitors in Oral Squamous Cell Carcinoma.

Jiang M, Li B Cells. 2022; 11(19).

PMID: 36231093 PMC: 9563058. DOI: 10.3390/cells11193131.

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