RNA interference-directed caveolin-1 knockdown sensitizes SN12CPM6 cells to doxorubicin-induced apoptosis and reduces lung metastasis

Juwon Park, Eunkyung Bae, Chansu Lee, Sung Soo Yoon, Yang Seok Chae, Kwang Sung Ahn, Nam Hee Won

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Human renal cell carcinoma (HRCC) is characterized by a high level of resistance to all treatment modalities. Therefore, the investigation of global gene expression in HRCC might help understand its biologic behavior and develop treatment strategies. Using cDNA microarray analysis, we initially compared gene expression profiles between HRCCs and adjacent normal tissues, and found that 87 were up-regulated and 127 genes were down-regulated. Next, a subset of genes, twofold differentially expressed, were validated by Northern blotting. Unexpectedly, caveolin-1, a gene reported to be a tumor suppressor gene, was found to be up-regulated in HRCC tissues. Expression level of caveolin-1 in SN12CPM6 (high metastatic clone) was higher than in SN12C (low metastatic clone), and SN12CPM6 was more resistant to doxorubicin (DXR) than SN12C. Caveolin-1 gene was slightly induced in surviving SN12C cells after DXR treatment. Furthermore, SN12CPM6-siCav1 cells, which were transfected with siRNA of cavelon-1 gene, were more sensitive to DXR, compared to SN12CPM6, but reduction of caveolin-1 gene expression did not affect tumor formation in subcapsule of kidney and lung metastasis. On the other hand, induction of caveolin-1 gene affected the production of lung metastasis under anti-cancer drug treatment: the incidence of pulmonary metastasis was significantly lower in SCID mice injected with SN12CPM6-siCav1 cells, and the number of pulmonary nodules decreased significantly (p=0.0004). The above results together suggest that caveolin-1 may confer a growth advantage to cancer cells during DXR chemotherapy and surviving HRCC cells eventually might develop lung metastasis.

Original languageEnglish
Pages (from-to)643-650
Number of pages8
JournalTumor Biology
Volume31
Issue number6
DOIs
Publication statusPublished - 2010 Dec

Keywords

  • Caveolin-1
  • Chemoresistance
  • Distant metastasis
  • Human renal cell carcinoma
  • Orthothopic animal model

ASJC Scopus subject areas

  • Cancer Research

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