Local Anesthetic Ropivacaine Exhibits Therapeutic Effects in Cancers

Abstract

Despite the significant progress in cancer treatment, new anticancer therapeutics drugs with new structures and/or mechanisms are still in urgent need to tackle many key challenges. Drug repurposing is a feasible strategy in discovering new drugs among the approved drugs by defining new indications. Recently, ropivacaine, a local anesthetic that has been applied in clinical practice for several decades, has been found to possess inhibitory activity and sensitizing effects when combined with conventional chemotherapeutics toward cancer cells. While its full applications and the exact targets remain to be revealed, it has been indicated that its anticancer potency was mediated by multiple mechanisms, such as modulating sodium channel, inducing mitochondria-associated apoptosis, cell cycle arrest, inhibiting autophagy, and/or regulating other key players in cancer cells, which can be termed as multi-targets/functions that require more in-depth studies. In this review, we attempted to summarize the research past decade of using ropivacaine in suppressing cancer growth and sensitizing anticancer drugs both in-vitro and in-vivo, and tried to interpret the underlying action modes. The information gained in these findings may inspire multidisciplinary efforts to develop/discover more novel anticancer agents via drug repurposing.

Ropivacaine enhanced the cisplatin-sensitivity of Human colorectal cancer cells by accelerating ROS-meditated apoptosis and ferroptosis

“…Besides, ropivacaine has been found to have inhibitory activity and sensitizing effects when used in combination with conventional chemotherapeutics toward cancer cells, but the speci c mechanism remains unclear [27]. Ropivacaine inhibited the growth and progression of various tumors through multiple pathways, a study conducted by Baptista-Hon et al reported that ropivacaine blocked the NaV1.5 VGSC in colon cancer cells to inhibit the invasion [28], and it also has signi cant antitumor effects on primary (SW480) and metastatic (SW620) colon cancer cells [29], those studies suggested that ropivacaine has a potential application in controlling colon cancer growth.…”

Ropivacaine represses the ovarian cancer cell stemness and facilitates cell ferroptosis through inactivating the PI3K/AKT signaling pathway

“…21 Ropivacaine has an antitumor role in various human tumors. 22 However, the ropivacaine role in ovarian cancer remained uncertain. In this study, we treated ovarian cancer cell lines with different doses of ropivacaine and demonstrated that ropivacaine inhibited ovarian cancer cell growth, implying that ropivacaine might exert a protective role in ovarian cancer.…”

Combinatorial Therapy of Cancer: Possible Advantages of Involving Modulators of Ionic Mechanisms

“…The pre-clinical case seemed strong, with LAs suppressing the viability and migratory capacity of breast cancer cells, dependent on the concentration and duration of drug application [ 12 , 13 , 14 , 15 ]. At least a part of the suppressive effect of LAs could occur via VGSC inhibition [ 16 ]. Disappointingly, however, regional anesthesia with lidocaine during tumor resection did not appear to have a significant effect on breast cancer outcomes including recurrence [ 17 ].…”