Ropivacaine inhibits the migration of esophageal cancer cells via sodium-channel-independent but prenylation-dependent inhibition of Rac1/JNK/paxillin/FAK

Zhang, Yaqin; Peng, Xiaohong; Zheng, Qinghong

doi:10.1016/j.bbrc.2018.05.110

Cited by 34 publications

(43 citation statements)

References 29 publications

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Section: Discussionmentioning

confidence: 99%

“…High concentrations of local anaesthetics have demonstrated an anti‐cancer effect . Whether these high levels are achieved when the local anaesthetic is infused into the peritoneal cavity is not known . In the original RCT, patients who received IPLA had lower serum levels of interleukin‐6, interleukin‐8 and tumour necrosis factor‐alpha, indicating a significant systemic anti‐inflammatory effect .…”

Section: Discussionmentioning

confidence: 99%

“…Surgical treatment is associated with considerable morbidity which can have long‐term effects on a patient's functionality and quality of life. Local anaesthetic drugs have been shown to have anti‐proliferative effect on colon cancer cells in vitro but this has not been evaluated in the clinical setting . In recent years interest in the delivery of intraperitoneal local anaesthetic (IPLA) has grown.…”

Section: Introductionmentioning

confidence: 99%

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Association between perioperative intraperitoneal local anaesthetic infusion and long‐term survival and cancer recurrence after colectomy: follow‐up analysis of a previous randomized controlled trial

MacFater

Xia

Barazanchi

et al. 2020

ANZ Journal of Surgery

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Background: High concentrations of local anaesthetic have an anti-proliferative effect on colonic cancer in vitro. Intraperitoneal local anaesthetic (IPLA) has shown analgesic benefit and improved recovery in the perioperative setting. The long-term effects of IPLA in colon cancer resection have not been examined. This study aims to review the survival and oncological outcomes of a previously conducted trial that compared perioperative IPLA with placebo. Methods: Sixty patients underwent colonic resection for benign and malignant disease as part of a double-blinded, randomized, placebo-controlled study between September 2008 and November 2009. The IPLA group received instillation of intraperitoneal ropivacaine before dissection followed by a 3-day infusion. The placebo group was treated identically but with 0.9% saline solution. A follow-up analysis was conducted to evaluate overall survival, disease-free survival and recurrence specifically for patients undergoing resection for stages I-III colon cancer. Kaplan-Meier analysis was performed, and the log-rank test was used to evaluate difference in survival between groups. Results: Thirty-seven of the 60 patients had stages I-III colon cancer and were included in this analysis. Nineteen patients were in the placebo group. There was no significant difference in overall survival or all-cause mortality. There was a higher incidence of cancerspecific mortality in the local anaesthetic group (P < 0.046). Conclusion: It does not appear that IPLA is associated with a significant survival benefit in patients with colonic malignancy undergoing colectomy. Other studies are needed to analyse the long-term outcomes.© 2020 Royal Australasian College of Surgeons ANZ J Surg 90 (2020) 802-806ANZJSurg.com

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between perioperative intraperitoneal local anaesthetic infusion and long‐term survival and cancer recurrence after colectomy: follow‐up analysis of a previous randomized controlled trial

MacFater

Xia

Barazanchi

et al. 2020

ANZ Journal of Surgery

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“…Migration assay was performed using the Boyden chamber (Cell Biolabs Inc. US) with transwell inserts of 8 μm pore size as described in our previous study [17]. The migrated cells from five random fields were counted under the microscope (Zeiss, Germany).…”

Section: Measurement Of Cell Apoptosis and Migrationmentioning

confidence: 99%

“…Rac1 [17]. To understand the molecular mechanism of ropivacaine's action in melanoma cells, we investigated the effects of ropivacaine on small GTPases.…”

Section: Ropivacaine and Lidocaine But Not Bupivacaine Augments The Imentioning

confidence: 99%

Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade

2020

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Background: Substantial clinical and preclinical evidence have indicated the association between amide-linked local anesthesia and the long-term outcomes of cancer patients. However, the potential effects of local anesthesia on cancer recurrence are inconclusive and the underlying mechanisms remain poorly understood. Methods: We systematically examined the effects of three commonly used local anesthetics in melanoma cells and analyzed the underlying mechanisms focusing on small GTPases. Results: Ropivacaine and lidocaine but not bupivacaine inhibited migration and proliferation, and induced apoptosis in melanoma cells. In addition, ropivacaine and lidocaine but not bupivacaine significantly augmented the in vitro efficacy of vemurafenib (a B-Raf inhibitor for melanoma with BRAF V600E mutation) and dacarbazine (a chemotherapeutic drug). Mechanistically, ropivacaine but not bupivacaine decreased the activities of Ras superfamily members with the dominant inhibitory effects on RhoA and Ras, independent of sodium channel blockade. Rescue studies using constitutively active Ras and Rho activator calpeptin demonstrated that ropivacaine inhibited migration mainly through RhoA whereas growth and survival were mainly inhibited through Ras in melanoma cells. We further detected a global reduction of downstream signaling of Ras and RhoA in ropivacainetreated melanoma cells. Conclusion: Our study is the first to demonstrate the anti-melanoma activity of ropivacaine and lidocaine but not bupivacaine, via targeting small GTPases. Our findings provide preclinical evidence on how amide-linked local anesthetics could affect melanoma patients.

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Ropivacaine inhibits tumor angiogenesis via sodium-channel-independent mitochondrial dysfunction and oxidative stress

Yang

Bao

et al. 2019

J Bioenerg Biomembr

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Ropivacaine inhibits the migration of esophageal cancer cells via sodium-channel-independent but prenylation-dependent inhibition of Rac1/JNK/paxillin/FAK

Cited by 34 publications

References 29 publications

Association between perioperative intraperitoneal local anaesthetic infusion and long‐term survival and cancer recurrence after colectomy: follow‐up analysis of a previous randomized controlled trial

Association between perioperative intraperitoneal local anaesthetic infusion and long‐term survival and cancer recurrence after colectomy: follow‐up analysis of a previous randomized controlled trial

Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade

Ropivacaine inhibits tumor angiogenesis via sodium-channel-independent mitochondrial dysfunction and oxidative stress

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