Autophagy inhibition of cancer stem cells promotes the efficacy of cisplatin against non-small cell lung carcinoma

Background: Clinical treatment of non-small cell lung carcinoma (NSCLC) by cisplatin eventually results in drug resistance, which cancer stem cells and autophagy are believed to be involved in. In the present study, we aimed to explore the effect of autophagy-inhibited cancer stem cells in NSCLC. Methods: Cancer stem cells were identified by CD133 expression levels detected by immunochemistry, real-time polymerase chain reaction, western blot, and flow cytometry. Stemness was detected by sphere-forming assays of tumor cells. Autophagy was determined by LC3-II expression at mRNA and protein levels. The effect of chloroquine (CQ) on autophagy was detected by real-time polymerase chain reaction, western blot and sphere-forming assay in vitro, and tumor growth in male NOD/SCID mice. Results: Cisplatin (CDDP) treatment enhanced CD133+ cell ratios in clinical NSCLC specimens and NSCLC cell line A549. The CD133+ cells enriched by CDDP exhibited higher autophagy levels. Autophagy inhibition by CQ inhibited CD133+ stemness and promoted CDDP efficiency in A549 cells. In addition, the combination of CDDP and CQ treatment significantly inhibited autophagy levels and cancer stem cell proportions in vitro, and dramatically suppressed tumor growth compared with individual agents. Conclusion: Autophagy inhibition of cancer stem cells could promote the efficacy of cisplatin against NSCLC. The reviews of this paper are available via the supplemental material section.

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Curcumin Targets Circulating Cancer Stem Cells by Inhibiting Self-Renewal Efficacy in Non-Small Cell Lung Carcinoma

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520616666160923102549 ◽

2017 ◽

Vol 17 (6) ◽

Cited By ~ 5

Author(s):

Sheefa Mirza ◽

Aakanksha Vasaiya ◽

Hemangini Vora ◽

Nayan Jain ◽

Rakesh Rawal

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Self Renewal ◽

Cell Lung Carcinoma

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Immunohistochemical Study Using Monoclonal VE1 Antibody Can Substitute the Molecular Tests for Apprehension of BRAF V600E Mutation in Patients with Non-small-Cell Lung Carcinoma

Analytical Cellular Pathology ◽

10.1155/2019/2315673 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Hadeel Abdul Elah Karbel ◽

Sura Salman Ejam ◽

Ali Zaki Naji

Keyword(s):

Polymerase Chain Reaction ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Braf V600e Mutation ◽

Braf V600e ◽

Small Cell Lung ◽

Chain Reaction ◽

Cell Lung Carcinoma ◽

Polymerase Chain

In patients with non-small-cell lung carcinoma (NSCLC), the analysis of BRAF V600E mutation has become more and more applied since the introduction of many mutation-targeted medications. In this regard, the advantage of immunohistochemistry (IHC) as a reliable diagnostic test substitute to other molecular studies has not been approved yet. Objective. To examine the dependability of using immunohistochemical method utilizing monoclonal VE1 antibody in the detection of BRAF V600 E mutation in patients with non-small-cell lung carcinoma and compare the results there with that of polymerase chain reaction (SSCP-PCR). Materials and Methods. We retrospectively identified 53 patients of whom their histopathological diagnosis was non-small-cell carcinoma of different types. Evaluation of BRAF V600E mutation was assessed using polymerase chain reaction (SSCP-PCR) and IHC using VE1 antibody. This approach was applied to all cases under the study. Results. Among the 53 NSCLC samples, only 5 (9.3%) cases harbored BRAF V600E mutation, 80% were of adenocarcinoma type, and the rest (20%) was of squamous cell carcinoma. IHC analysis for VE1 was positive in 4 out of 5 (80%) BRAF-mutated tumors and negative in all nonmutated BRAF V600 E NSCLC. Conclusion. Our results revealed that VE1 antibody IHC analysis is a promising technique that can be used to detect BRAF V600-mutated NSCLC with relatively high specificity and sensitivity and might become a potential alternative to the current molecular biological methods that are in use for this purpose.

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