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Pirfenidone Sensitizes NCI-H460 Non-Small Cell Lung Cancer Cells to Paclitaxel and to a Combination of Paclitaxel with Carboplatin.

ABSTRACT: Pirfenidone, an antifibrotic drug, has antitumor potential against different types of cancers. Our work explored whether pirfenidone sensitizes non-small cell lung cancer (NSCLC) cell lines to chemotherapeutic treatments. The cytotoxic effect of paclitaxel in combination with pirfenidone against three NSCLC cell lines (A549, NCI-H322 and NCI-H460) was evaluated using the sulforhodamine B assay. The effects of this combination on cell viability (trypan blue exclusion assay), proliferation (BrdU incorporation assay), cell cycle (flow cytometry following PI staining) and cell death (Annexin V-FITC detection assay and Western blot) were analyzed on the most sensitive cell line (NCI-H460). The cytotoxic effect of this drug combination was also evaluated against two non-tumorigenic cell lines (MCF-10A and MCF-12A). Finally, the ability of pirfenidone to sensitize NCI-H460 cells to a combination of paclitaxel plus carboplatin was assessed. The results demonstrated that pirfenidone sensitized NCI-H460 cells to paclitaxel treatment, reducing cell growth, viability and proliferation, inducing alterations in the cell cycle profile and causing an increase in the % of cell death. Remarkably, this combination did not increase cytotoxicity in non-tumorigenic cells. Importantly, pirfenidone also sensitized NCI-H460 cells to paclitaxel plus carboplatin. This work highlights the possibility of repurposing pirfenidone in combination with chemotherapy for the treatment of NSCLC.

SUBMITTER: Branco H

PROVIDER: S-EPMC8998757 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Pirfenidone Sensitizes NCI-H460 Non-Small Cell Lung Cancer Cells to Paclitaxel and to a Combination of Paclitaxel with Carboplatin.

Branco Helena H Oliveira Júlio J Antunes Catarina C Santos Lúcio L LL Vasconcelos Maria Helena MH Xavier Cristina P R CPR

International journal of molecular sciences 20220326 7

Pirfenidone, an antifibrotic drug, has antitumor potential against different types of cancers. Our work explored whether pirfenidone sensitizes non-small cell lung cancer (NSCLC) cell lines to chemotherapeutic treatments. The cytotoxic effect of paclitaxel in combination with pirfenidone against three NSCLC cell lines (A549, NCI-H322 and NCI-H460) was evaluated using the sulforhodamine B assay. The effects of this combination on cell viability (trypan blue exclusion assay), proliferation (BrdU i ...[more]

PMID: 35408988

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Project description:In both males and females, lung cancer is one of the most lethal cancers worldwide and accounts for >30% of cancer-related deaths. Despite advances in biomarker analysis and tumor characterization, there remains a need to find suitable biomarker antigen targets for treatment in late-stage lung cancer. Previous research on the salvage pathway enzyme TK1 shows a unique relationship with cancer patients as serum levels are raised according to cancer grade. To expand this analysis, the other salvage pathway enzymes were evaluated for possible upregulation within lung cancer. Adenine phosphoribosyltransferase, deoxycytidine kinase, and hypoxanthine guanine phosphoribosyltransferase (HPRT) were assessed for their presentation on two non-small-cell lung cancer cell lines NCI-H460 and A549. In the present study, we show that deoxycytidine kinase and adenine phosphoribosyltransferase have no significant relationship with the membrane of NCI-H460 cells. However, we found significant localization of HPRT to the membrane of NCI-H460 and A549 cells. When treated with anti-HPRT antibodies, the average fluorescence of the cell population increased by 24.3% and 12.9% in NCI-H460 and A549 cells, respectively, in comparison with controls. To ensure that expression was not attributed to cytoplasmic HPRT, confocal microscopy was performed to visualize HPRT binding on the plasma membrane. After staining NCI-H460 cells treated with both fluorescent antibodies and a membrane-specific dye, we observed direct overlap between HPRT and the membrane of the cancer cells. Additionally, gold-conjugated antibodies were used to label and quantify the amount of HPRT on the cell surface using scanning electron microscopy and energy-dispersive analysis X-ray. Further confirming HPRT presence, the gold weight percentage of the sample increased significantly when NCI-H460 cells were exposed to HPRT antibody (P=0.012) in comparison with isotype controls. Our results show that HPRT is localized on the surface of these non-small-cell lung cancer cell lines.

Dataset Information

Pirfenidone Sensitizes NCI-H460 Non-Small Cell Lung Cancer Cells to Paclitaxel and to a Combination of Paclitaxel with Carboplatin.

Publications

Pirfenidone Sensitizes NCI-H460 Non-Small Cell Lung Cancer Cells to Paclitaxel and to a Combination of Paclitaxel with Carboplatin.

Similar Datasets

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