Acquisition of an enhanced aggressive phenotype in human lung cancer cells selected by suboptimal doses of cisplatin following cell deattachment and reattachment

Jeng Long Hsieh, Chia Sing Lu, Chin Ling Huang, Gia Shing Shieh, Bing Hua Su, Yu Chu Su, Che Hsin Lee, Meng Ya Chang, Chao Liang Wu, Ai Li Shiau

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Chemotherapy is one major approach for treating non-small cell lung carcinoma (NSCLC). However, the progression-free survival rate depends on whether there is tumor metastasis after drug treatment. The biological behavior for its characteristics remains to be clarified. Here, we treated A549 and H1299 NSCLC cell lines with cisplatin, doxorubicin and gemcitabine at the IC 50 dose. Most attached cells were surviving cells (A549-A and H1299-A), whereas only a small portion of detached cells survived and reattached to tissue culture plates (A549-R and H1299-R) for further growth. Using cisplatin, a series of H1299 sublines (H1299-R2~H1299-R5) were also generated by the same selection procedure. Drug treatment increased the migratory ability of A549-R and H1299-R cells. A serial selection could enhance the invasiveness of cells. Cisplatin treatment inhibited the adhesion ability of H1299-R cells compared with their H1299 and H1299-A counterparts. H1299-R cells exhibited increased drug resistance to cisplatin and increased expression of ABCG2, CD133 and CD44. Compared with mice subcutaneously injected with H1299 cells, mice subcutaneously injected with H1299-R cells showed an increase in the number of metastatic lung nodules. We conclude that H1299-R cells selected by suboptimal doses of cisplatin following detachment from and reattachment to the tissue culture plate acquire an enhanced malignant phenotype. Therefore, they provide a more faithful lung cancer model associated with biological aggressiveness for studying clinically recurrent cancers after chemotherapy.

Original languageEnglish
Pages (from-to)36-44
Number of pages9
JournalCancer Letters
Volume321
Issue number1
DOIs
Publication statusPublished - 2012 Aug 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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