Combination therapy with ropivacaine-loaded liposomes and nutrient deprivation for simultaneous cancer therapy and cancer pain relief

Zhang, Jiqian; Zhu, Shasha; Tan, Qilian; Cheng, Dan; Dai, Qingqing; Yang, Zhilai; Zhang, Lei; Li, Fenfen; Zuo, You-Mei; Dai, Wei; Chen, Lihai; Gu, Erwei; Xu, Gaowei; Wei, Zhaolian; Cao, Yunxia; Liu, Xuesheng

doi:10.7150/thno.43932

Cited by 30 publications

(27 citation statements)

References 58 publications

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“…Ropivacaine has been shown to play an effective role in different cancer therapies by inhibiting cell proliferation, migration, invasion, and inducing apoptosis [ 17 , 18 ]. Combination therapy with nutrient deprivation and ropivacaine, which is loaded into tumor-active targeted liposomes, contributes to tumor growth inhibition and cancer pain remission [ 19 ]. Local anesthetic ropivacaine may negatively affect tumor reoccurrence and lung tumor metastasis by inducing mitochondrial dysfunction [ 20 ].…”

Section: Inductionmentioning

confidence: 99%

Ropivacaine suppresses tumor biological characteristics of human hepatocellular carcinoma via inhibiting IGF-1R/PI3K/AKT/mTOR signaling axis

et al. 2021

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Ropivacaine, a common local anesthetic in the clinic, has anti-proliferative and pro-apoptotic effects in numerous cancers, however, the underlying regulatory mechanism of ropivacaine in hepatocellular carcinoma remains unclear. In the current study, human HepG2 cells were stimulated with different ropivacaine concentrations. Cell Counting Kit-8 assay, cell colony formation, and cell cycle were used to monitor cell viability. Cell apoptosis, migration, and invasion were determined by flow cytometry and transwell assays. Tumor xenograft experiments were performed to prove the anti-cancer effect of ropivacaine in vivo . A high dose of ropivacaine inhibited proliferation and promoted apoptosis of HepG2 cells in a dose-dependent manner. Ropivacaine challenge also arrested cells in the G2 phase, followed by a decline in the protein expression of cyclin D1 and cyclin-dependent kinase 2, and an increase in p27 levels in HepG2 cells. Additionally, different ropivacaine doses suppressed cell migration and invasion by upregulating E-cadherin expression and downregulating N-cadherin expression. Mechanically, ropivacaine challenge gradually restrained insulin-like growth factor-1 receptor (IGF-1 R) expression and the activities of phosphorylated-PI3K, AKT, and mTOR in HepG2 cells with increased ropivacaine doses. In the tumor xenograft experiment, ropivacaine was confirmed to inhibit tumor growth, accompanied by inhibition of the IGF-1 R/PI3K/AKT/mTOR signaling axis. In conclusion, ropivacaine suppressed tumor biological characteristics and promoted apoptosis, resulting in the suppression of hepatocellular carcinoma progression by targeting the IGF-1 R/PI3K/AKT/mTOR signaling pathway. It is possible that ropivacaine-mediated local anesthesia may be developed as a novel surgical adjuvant drug for treating hepatocellular carcinoma.

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Section: Inductionmentioning

confidence: 99%

Ropivacaine suppresses tumor biological characteristics of human hepatocellular carcinoma via inhibiting IGF-1R/PI3K/AKT/mTOR signaling axis

et al. 2021

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“…So et al found that midazolam can induce apoptosis of Leydig tumor cells by regulating autophagy [20]. Zhang et al also found that ropivacaine can inhibit the growth of melanoma [21]. Since these autophagy inhibitors have not been widely used in clinical treatment, their safety and potential molecular mechanisms related to ESCA are unclear.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Autophagy-related LncRNAs in Esophageal Carcinoma

Fan

Ding

2020

Preprint

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Background: Esophageal carcinoma (ESCA) is a malignant tumor with high invasiveness and mortality. Autophagy has multiple roles in the development of cancer; however, there are limited data on autophagy genes associated with long non-coding RNAs (lncRNAs) in ESCA. The purpose of this study was to screen potential diagnostic and prognostic molecules, and to identify gene co-expression networks associated with autophagy in ESCA. Methods: We downloaded transcriptome expression profiles from The Cancer Genome Atlas and autophagy-related gene data from the Human Autophagy Database, and analyzed the co-expression of mRNAs and lncRNAs. In addition, the diagnostic and prognostic value of autophagy-related lncRNAs was analyzed by multivariate Cox regression. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis was carried out for high-risk patients, and enriched pathways were analyzed by gene set enrichment analysis. Results: The results showed that genes of high-risk patients were enriched in protein export and spliceosome. Based on Cox stepwise regression and survival analysis, we identified seven autophagy-related lncRNAs with prognostic and diagnostic value, with the potential to be used as a combination to predict the prognosis of patients with ESCA. Finally, a co-expression network related to autophagy was constructed. Conclusion: These results suggest that autophagy-related lncRNAs and the spliceosome play important parts in the pathogenesis of ESCA. Our findings provide new insight into the molecular mechanism of ESCA and suggest a new method for improving its treatment.

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“…Combinational therapy of ropivacaine has also been attempted to inhibit pain relief and tumor growth simultaneously. Zhang et al (20) developed a formulation of liposomes composed with ropivacaine (named as Rop-DPRL), and these liposomes, when combined with nutrition deprivation which may lead to activated autophagy, can suppress the tumor growth of melanoma B16 cells xenograft model and relieve the cancer pain (60). Further study indicated that these effects were mediated by reducing the expression of VEGF-A, and inhibiting the phosphorylation of STAT3 (60).…”

Section: Via Regulating Autophagy Through Vascular Endothelial Growth...mentioning

confidence: 99%

Local Anesthetic Ropivacaine Exhibits Therapeutic Effects in Cancers

Zhang

Tan

et al. 2022

Front. Oncol.

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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.

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Combination therapy with ropivacaine-loaded liposomes and nutrient deprivation for simultaneous cancer therapy and cancer pain relief

Cited by 30 publications

References 58 publications

Ropivacaine suppresses tumor biological characteristics of human hepatocellular carcinoma via inhibiting IGF-1R/PI3K/AKT/mTOR signaling axis

Ropivacaine suppresses tumor biological characteristics of human hepatocellular carcinoma via inhibiting IGF-1R/PI3K/AKT/mTOR signaling axis

Bioinformatics Analysis of Autophagy-related LncRNAs in Esophageal Carcinoma

Local Anesthetic Ropivacaine Exhibits Therapeutic Effects in Cancers

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