Both Bupivacaine and Levobupivacaine inhibit colon cancer cell growth but not melanoma cells in vitro.

Abstract

BACKGROUND:

Retrospective studies indicate that the use of regional anaesthesia causes a reduction in cancer recurrence after oncological surgery, which could be due to anaesthetic's negating effect on immunosuppression related to the surgical stress response. Local anaesthetics may also exert direct suppressive effects on malignant cells, an area where further investigation is urgently needed.

METHODS:

Human colon cancer cells and human melanoma cells were cultured and then treated with 1 mM bupivacaine or levobupivacaine for up to 24 or 48 h. Their migratory ability was measured by scratch assay, proliferation determined with Ki67 immunofluorescence staining, and apoptosis accessed with annexin V and PI staining on flow cytometry. The effects of bupivacaine and levobupivacaine on cellular signaling and molecular response, specifically, on endoplasmic reticulum stress (ERS), were studied with immunostaining and western blot.

RESULTS:

In colon cancer cells, treatment with bupivacaine and levobupivacaine significantly inhibited cell migration (**p < 0.01, ***p < 0.001; n = 4) and proliferation (**p < 0.01; n = 4), while increasing the expression of CHOP (***p < 0.001; n = 4) and decreased the expression of Grp78 (*p < 0.05; n = 4). These effects were not mirrored by melanoma cells, such that no significant increase in apoptosis was seen in either melanoma cell lines following treatment.

CONCLUSION:

These in vitro data suggested that both bupivacaine and levobupivacaine suppress colorectal adenocarcinoma cell proliferation and migration, which are concurrent with increased endoplasmic reticulum stress. Conversely, melanoma cells are more resilient to these two commonly used local anaesthetics. Further in vivo studies or clinical trials are needed.

• Authors: Tianci Li, Lin Chen, Hailin Zhao, Lingzhi Wu, Joe Masters, Chongfang Han, Kazuyoshi Hirota, Daqing Ma
• Journal: Journal of anesthesia (J Anesth) Vol. 33 Issue 1 Pg. 17-25 (02 2019) ISSN: 1438-8359 [Electronic] Japan
• PMID: 30426213 (Publication Type: Journal Article)

Chemical References

• Anesthetics, Local
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Levobupivacaine
• Bupivacaine

Topics

• Anesthetics, Local (pharmacology)
• Apoptosis (drug effects)
• Bupivacaine (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy)
• Endoplasmic Reticulum Chaperone BiP
• Humans
• Levobupivacaine (pharmacology)
• Melanoma (drug therapy)