The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling

Gu, Jianhua; Liu, Cuicui; Xie, Jin-Lan; Ma, Baochun; Cui, Shaomin; Yang, Guang-Zhu; He, Shun-Cheng

doi:10.3389/fonc.2021.616445

Cited by 12 publications

(11 citation statements)

References 32 publications

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“…Recently, several works have described the adjuvant anticancer action of local anesthetics such as LDC [19,20], bupivacaine [21][22][23][24] and ropivacaine [25]. LDC can suppress cancer cell growth (in vitro and in vivo) through several mechanisms: regulation of epigenetic changes, promotion of pro-apoptotic pathways and regulation of ABC transporters, also preventing metastasis and angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma

et al. 2021

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Melanoma is the most aggressive skin carcinoma and nanotechnology can bring new options for its pharmacological treatment. Nanostructured lipid carriers (NLC) are ideal drug-delivery carriers for hydrophobic drugs, such as the antineoplastic docetaxel (DTX), and hybrid (NLC-in-hydrogel) systems are suitable for topical application. This work describes a formulation of NLCDTX in xanthan-chitosan hydrogel containing lidocaine (LDC) with anticancer and analgesia effects. The optimized nanoparticles encapsulated 96% DTX and rheological analysis revealed inherent viscoelastic properties of the hydrogel. In vitro assays over murine fibroblasts (NIH/3T3) and melanoma cells (B16-F10), human keratinocytes (HaCaT) and melanoma cells (SK-MEL-103) showed reduction of docetaxel cytotoxicity after encapsulation in NLCDTX and HGel-NLCDTX. Addition of LDC to the hybrid system (HGel-NLCDTX-LDC) increased cell death in tumor and normal cells. In vivo tests on C57BL/6J mice with B16-F10-induced melanoma indicated that LDC, NLCDTX, HGel-NLCDTX-LDC and NLCDTX + HGel-LDC significantly inhibited tumor growth while microPET/SPECT/CT data suggest better prognosis with the hybrid treatment. No adverse effects were observed in cell survival, weight/feed-consumption or serum biochemical markers (ALT, AST, creatinine, urea) of animals treated with NLCDTX or the hybrid system. These results confirm the adjuvant antitumor effect of lidocaine and endorse HGel-NLCDTX-LDC as a promising formulation for the topical treatment of melanoma.

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Section: Introductionmentioning

confidence: 99%

Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma

et al. 2021

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“…Researchers found that autophagy played a vital role in tumorigenesis and development. Gu et al confirmed that bupivacaine-induced autophagy through Akt/mTOR signaling, inhibiting the progression of NSCLC (Gu et al, 2021). Lin et al proposed that high expression of miR-30a improved the prognosis of NSCLC after neoadjuvant chemotherapy by reducing autophagy caused by chemotherapy drugs (Lin et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma

Chen

Sang

et al. 2021

Front. Genet.

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Autophagy is closely associated with the tumor immune microenvironment (TIME) and prognosis of patients with lung adenocarcinoma (LUAD). In the present study, we established a signature on the basis of long noncoding RNAs (lncRNAs) related to autophagy (ARlncRNAs) to investigate the TIME and survival of patients with LUAD. We selected ARlncRNAs associated with prognosis to construct a model and divided each sample into different groups on the basis of risk score. The ARlncRNA signature could be recognized as an independent prognostic factor for patients with LUAD, and patients in the low-risk group had a greater survival advantage. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis suggested that several immune functions and pathways were enriched in different groups. A high-risk score correlated significantly negatively with high abundance of immune cells and stromal cells around the tumor and high tumor mutational burden. Low-risk patients had a higher PD-1, CTLA-4, and HAVCR2 expression and had a better efficacy of immune checkpoint inhibitors, including PD-1/CTLA-4 inhibitor. A reliable signature on the basis of ARlncRNAs was constructed to explore the TIME and prognosis of patients with LUAD, which could provide valuable information for individualized LUAD treatment.

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“…Interestingly, all these screen hits are linked to different processes of autophagy. Rapamycin is a well-studied mTOR inhibitor that triggers autophagy and ubiquitin-proteasome system [29]; Bupivacaine has been reported to induce protein degradation in muscle cells [30,31] and also induce autophagy in lung cancer cells [32]; ABT199 is a BCL2 inhibitor that has the potency to regulate apoptosis and autophagy pathway [33]. These data imply that manipulating protein-specific degradation is a plausible approach to inhibit PreS2-LHBS.…”

Section: Discussionmentioning

confidence: 99%

Chemical-induced degradation of PreS2 mutant surface antigen reverses HBV-mediated hepatocarcinogenesis

Yang

Pan

et al. 2022

Preprint

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Naturally evolved immune-escape PreS2 mutant is an oncogenic caveat of liver cirrhosis and hepatocellular carcinoma (HCC) during chronic hepatitis B virus (HBV) infection. Notably, PreS2 mutants is prevalent in above 50% of patients with HCC. Intrahepatic expression of PreS2 mutant large surface antigen (PreS2-LHBS) induces endoplasmic reticulum stress, mitochondria dysfunction, cytokinesis failure and subsequent chromosome hyperploidy. In this study, we ask if long-term inhibition of PreS2-LHBS may act to reverse HBV-mediated hepatocarcinogenesis. We set up a stability reporter platform and identified ABT199 as an inhibitor of PreS2-LHBS from a library of 1068 FDA-approved drugs. Treatment of ABT199 induced PreS2-LHBS degradation without affecting the general cell viability, as shown in hepatoma and immortalized hepatocyte cell lines. We found that ABT199 induced the recruitment of PreS2-LHBS to ring-shaped structures in close proximity to lysosomal marker Lamp1 and multivesicular body marker Rab7. Simultaneously, inhibitions of lysosomal degradation or microautophagy restored the expression of PreS2-LHBS. Specifically, a 24-hr treatment of ABT199 reduced DNA damages and cytokinesis failure induced by PreS2-LHBS. Persistent treatment of ABT199 for 3 weeks reversed chromosome hyperploidy in PreS2-LHBS cells and suppressed anchorage-independent growth of HBV-positive hepatoma cell line. Together, we showed that ABT199 provoked selective degradation of PreS2-LHBS through the induction of microautophagy, and a long-term treatment of ABT199 reversed oncogenic mechanisms induced by HBV. Our results indicate that long-term degradation of PreS2-LHBS may serve as a novel therapeutic strategy to constrain HBV-mediated hepatocarcinogenesis.

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The Local Anesthetic Bupivacaine Inhibits the Progression of Non-Small Cell Lung Cancer by Inducing Autophagy Through Akt/mTOR Signaling

Cited by 12 publications

References 32 publications

Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma

Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma

Chemical-induced degradation of PreS2 mutant surface antigen reverses HBV-mediated hepatocarcinogenesis

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