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Bupivacaine inhibits the malignant biological behavior of oral squamous cell carcinoma cells by inhibiting the activation of ERK1/2 and STAT3.
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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 in vitro 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 in vivo.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. In vivo, 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.
SUBMITTER: Wang Z
PROVIDER: S-EPMC8184410 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Bupivacaine inhibits the malignant biological behavior of oral squamous cell carcinoma cells by inhibiting the activation of ERK1/2 and STAT3.
Annals of translational medicine 20210501 10
<h4>Background</h4>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.<h4>Methods</h4>We selected OSCC CAL-27 cells as the <i>in vitro</i> 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 evalu ...[more]