Abstract
BackgroundBreast cancer accounts for nearly a quarter of all cancers in women worldwide, and more than 90% of women diagnosed with breast cancer undergo mastectomy or breast-conserving surgery. Retrospective clinical studies have suggested that use of regional anesthesia leads to improved patient outcomes. Laboratory studies have reported that breast cancer cells are inhibited by some local anesthetics at millimolar concentration. Here, we present a comprehensive analysis of the effects of six common local anesthetics on two human breast cancer cell lines. We used concentrations ranging from those corresponding to plasma levels during regional block by local anesthetic (plasma concentration) to those corresponding to direct infiltration of local anesthetic.MethodsHuman breast cancer cell lines, MDA-MB-231 and MCF7, were incubated with each of six local anesthetics (lidocaine, mepivacaine, ropivacaine, bupivacaine, levobupivacaine, and chloroprocaine) (10 μM ~ 10 mM) for 6 to 72 h. Assays for cell viability, cytotoxicity, migration, and cell cycle were performed.ResultsHigh concentrations (> 1 mM) of local anesthetics applied to either MDA-MB-231 or MCF7 cells for 48 h significantly inhibited cell viability and induced cytotoxicity. At plasma concentrations (~ 10 μM) for 72 h, none of the local anesthetics affected cell viability or migration in either cell line. However, at 10 × plasma concentrations, 72-h exposure to bupivacaine, levobupivacaine or chloroprocaine inhibited the viability of MDA-MB-231 cells by > 40% (p < 0.001). Levobupivacaine also inhibited the viability of MCF7 cells by 50% (p < 0.001). None of the local anesthetics affected the viability of a non-cancerous breast cell line, MCF10A. MDA-MB-231 cell migration was inhibited by 10 × plasma concentrations of levobupivacaine, ropivacaine or chloroprocaine and MCF7 cell migration was inhibited by mepivacaine and levobupivacaine (p < 0.05). Cell cycle analysis showed that the local anesthetics arrest MDA-MB-231 cells in the S phase at both 1 × and 10 × plasma concentrations.ConclusionsLocal anesthetics at high concentrations significantly inhibited breast cancer cell survival. At 10 × plasma concentrations, the effect of local anesthetics on cancer cell viability and migration depended on the exposure time, specific local anesthetic, specific measurement endpoint and specific cell line.
Highlights
Breast cancer accounts for nearly a quarter of all cancers in women worldwide, and more than 90% of women diagnosed with breast cancer undergo mastectomy or breast-conserving surgery
Viability of MDA-MB-231, MCF-7, and MCF10A cells treated with high doses of local anesthetics To establish the response of cancer cells treated with clinical preparation concentrations of local anesthetics, we exposed cells to concentrations ranging from 0.3 mM (30 times higher than the anti-arrhythmia plasma concentration of lidocaine) to 10 mM
Significant cell death was caused by 1 mM mepivicaine, levobupivacaine and chloroprocaine only but higher concentrations of all local anesthetics were effective at killing cells (Fig. 1b)
Summary
Breast cancer accounts for nearly a quarter of all cancers in women worldwide, and more than 90% of women diagnosed with breast cancer undergo mastectomy or breast-conserving surgery. Retrospective clinical studies have suggested that use of regional anesthesia leads to improved patient outcomes. Laboratory studies have reported that breast cancer cells are inhibited by some local anesthetics at millimolar concentration. We present a comprehensive analysis of the effects of six common local anesthetics on two human breast cancer cell lines. Breast cancer is one of the most common types of cancer and the second leading cause of cancer death in women. Surgery for breast cancer may be performed under general anesthesia with or without regional anesthesia. The addition of regional anesthesia in the form of a paravertebral block has been shown to be associated with a longer recurrence free period for patients with breast cancers following surgical resection [2]. Recent retrospective studies have shown that regional anesthesia
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