Evidence map›Paper›PMID 27840408›Full record

ArticleActa pharmacologica Sinica2016

Cathepsin L upregulation-induced EMT phenotype is associated with the acquisition of cisplatin or paclitaxel resistance in A549 cells.

Mei-Ling Han, Yi-Fan Zhao, Cai-Hong Tan, Ya-Jie Xiong, Wen-Juan Wang, Feng Wu, Yao Fei, Long Wang, Zhong-Qin Liang

Open access · bronzeAbstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 157 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Mei-Ling HanDepartment of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Yi-Fan ZhaoDepartment of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Cai-Hong TanDepartment of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Ya-Jie XiongDepartment of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Wen-Juan WangDepartment of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Feng WuDepartment of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China.
Yao FeiDepartment of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Long WangDepartment of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Zhong-Qin LiangDepartment of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Soochow University · CNAffiliated Hospital of Jiangsu University · CNNantong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimCathepsin L (CTSL), a lysosomal acid cysteine protease, is known to play important roles in tumor metastasis and chemotherapy resistance. In this study we investigated the molecular mechanisms underlying the regulation of chemoresistance by CTSL in human lung cancer cells.

methodsHuman lung cancer A549 cells, A549/PTX (paclitaxel-resistant) cells and A549/DDP (cisplatin-resistant) cells were tested. The resistance to cisplatin or paclitaxel was detected using MTT and the colony-formation assays. Actin remodeling was observed with FITC-Phalloidin fluorescent staining or immunofluorescence. A wound-healing assay or Transwell assay was used to assess the migration or invasion ability. The expression of CTSL and epithelial and mesenchymal markers was analyzed with Western blotting and immunofluorescence. The expression of EMT-associated transcription factors was measured with Western blotting or q-PCR. BALB/c nude mice were implanted subcutaneously with A549 cells overexpressing CTSL, and the mice were administered paclitaxel (10, 15 mg/kg, ip) every 3 d for 5 times.

resultsCisplatin or paclitaxel treatment (10-80 ng/mL) induced CTSL expression in A549 cells. CTSL levels were much higher in A549/PTX and A549/DDP cells than in A549 cells. Silencing of CTSL reversed the chemoresistance in A549/DDP and A549/TAX cells, whereas overexpression of CTSL attenuated the sensitivity of A549 cells to cisplatin or paclitaxel. Furthermore, A549/DDP and A549/TAX cells underwent morphological and cytoskeletal changes with increased cell invasion and migration abilities, accompanied by decreased expression of epithelial markers (E-cadherin and cytokeratin-18) and increased expression of mesenchymal markers (N-cadherin and vimentin), as well as upregulation of EMT-associated transcription factors Snail, Slug, ZEB1 and ZEB2. Silencing of CTSL reversed EMT in A549/DDP and A549/TAX cells; In contrast, overexpression of CTSL induced EMT in A549 cells. In xenograft nude mouse model, the mice implanted with A549 cells overexpressing CTSL exhibited significantly reduced sensitivity to paclitaxel treatment, and increased expression of EMT-associated proteins and transcription factors in tumor tissues.

conclusionCisplatin and paclitaxel resistance is associated with CTSL upregulation-induced EMT in A549 cells. Thus, CTSL-mediated EMT may be exploited as a target to enhance the efficacy of cisplatin or paclitaxel against lung cancer and other types of malignancies.

Indexed as

A549 CellsAnimalsAntineoplastic AgentsCathepsin LCisplatinDrug Resistance, NeoplasmHumansMaleMiceMice, Inbred BALB CPaclitaxelUp-RegulationAntineoplastic AgentsCathepsin LCisplatinPaclitaxel

Identifiers

PMID27840408
PMCPMC5309731
OpenAlexW2552678153

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.