Korean J Physiol Pharmacol.  2017 Sep;21(5):465-474. 10.4196/kjpp.2017.21.5.465.

Resveratrol raises in vitro anticancer effects of paclitaxel in NSCLC cell line A549 through COX-2 expression

• Kong F
• Zhang R
• Zhao X
• Zheng G
• Wang Z
• Wang P

• KMID: 2388692
• DOI: http://doi.org/10.4196/kjpp.2017.21.5.465

Abstract

The aim of this study was to determine the raising anticancer effects of resveratrol (Res) on paclitaxel (PA) in non-small cell lung cancer (NSCLC) cell line A549. The 10 µg/ml of Res had no effect on human fetal lung fibroblast MRC-5 cells or on A549 cancer cells and the 5 or 10 µg/ml of PA also had no effect on MRC-5 normal cells. PA-L (5 µg/ml) and PA-H (10 µg/ml) had the growth inhibitory effects in NSCLC cell line A549, and Res increased these growth inhibitory effects. By flow cytometry experiment, after Res (5 µg/ml)+PA-H (10 µg/ml) treatment, the A549 cells showed the most apoptosic cells compared to other group treatments, and after additional treatment with Res, the apoptosic cells of both two PA concentrations were raised. Res+PA could reduce the mRNA and protein expressions of COX-2, and Res+PA could reduce the COX-2 related genes of VEGF, MMP-1, MMP-2, MMP-9, NF-κB, Bcl-2, Bcl-xL, procollagen I, collagen I, collagen III and CTGF, TNF-α, IL-1β, iNOS and raise the TIMP-1, TIMP-2, TIMP-3, IκB-α, p53, p21, caspase-3, caspase-8, caspase-9, Bax genes compared to the control cells and the PA treated cells. From these results, it can be suggested that Res could raise the anticancer effects of PA in A549 cells, thus Res might be used as a good sensitizing agent for PA.

Keyword

A549; Cancer; Gene; Paclitaxel; Resveratrol

MeSH Terms

Carcinoma, Non-Small-Cell Lung
Caspase 3
Caspase 8
Caspase 9
Cell Line*
Collagen
Fibroblasts
Flow Cytometry
Humans
In Vitro Techniques*
Lung
Paclitaxel*
Procollagen
RNA, Messenger
Tissue Inhibitor of Metalloproteinase-1
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-3
Vascular Endothelial Growth Factor A
Caspase 3
Caspase 8
Caspase 9
Collagen
Paclitaxel
Procollagen
RNA, Messenger
Tissue Inhibitor of Metalloproteinase-1
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-3
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 Effect of resveratrol (A), paclitaxel (B) on the growth of human fetal lung fibroblast cells MRC -5, NSCLC cell line A549 and apoptosis inducing effects (DNA content of sub-G1) of resveratrol (Res) and paclitaxel (PA) in NSCLC cell line A549 (C).a~eMean values with different letters over the bars are significantly different (p<0.05) according to Duncan's multiplerange test. PA-L, 5 µg/ml of paclitaxel; Res+PA-L, 10 µg/ml of resveratrol+5 µg/ml of paclitaxel; PA-H, 10 µg/ml of paclitaxel; Res+PA-H, 10 µg/ml of resveratrol+10 µg/ml of paclitaxel.

• 

  Fig. 2 The mRNA and protein expression of COX-2, VEGF (A), MMP-2, MMP-9, TIMP-1, TIMP-2 (B) and mRNA expression of MMP-1, TIMP-3 (C) in NSCLC cell line A549.a~eMean values with different letters over the bars are significantly different (p<0.05) according to Duncan's multiple-range test.

• 

  Fig. 3 The mRNA and protein expression of NF-κB, IκB-α (A), p53, p21 (B), caspase-3, caspase-8, caspase-9 (C), Bax, Bcl-2 and Bcl-xL (D) in NSCLC cell line A549.a~eMean values with different letters over the bars are significantly different (p<0.05) according to Duncan's multiple-range test.

• 

  Fig. 4 The mRNA expression of procollagen I, collagen I, collagen III , CT GF (A), TNF-α, IL-1β, iNOS (B) in NSCLC cell line A549 and the mRNA expression of CO X-2 (C) in celecoxib (15 µg/ml) and Res+PA-H treated A549 cells.a~eMean values with different letters over the bars are significantly different (p<0.05) according to Duncan's multiple-range test.

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