Contribution of nitric oxide and epidermal growth factor receptor in anti-metastatic potential of paclitaxel in human liver cancer cell (HebG2).
BACKGROUND
Paclitaxel is a general antineoplastic drug used against different types of experimental and human tumors. Several anti-cancer drugs have been shown to stimulate nitric oxide (NO) production, which has been shown to affect many aspects of tumor biology.


OBJECTIVE
This study was initiated to determine if paclitaxel stimulates NO production in HebG2 cells, and if so, whether NO interferes with the metastatic potential of HebG2 cells and contributes to paclitaxel cytotoxicity. In addition, we sought to determine the relationship between NO production and the expression of epidermal growth factor receptor (EGFR) and matrix metaloproteinases (MMPs) in HebG2 cells.


METHODS
The effects of paclitaxel (0.1-1000 nM) on surviving fraction, NO production and the expression of EGFR, MMP-2 and MMP-9 were studied in human liver cancer cells (HebG2).


RESULTS
Paclitaxel resulted in a significant dose dependent decrease in the surviving fraction of HebG2 cells. A 62% and 86% decrease in the surviving fraction was attained at 10nM and 100 nM paclitaxel, respectively. Paclitaxel produced a significant increase in NO production, starting from 1 nM. A 64% and 111% increase in NO production was attained after exposure to 10nM and 100 nM of paclitaxel, respectively. In all of the HebG2 cells treated with paclitaxel (1.0-1000 nM) mRNA specific for EGFR, MMP-2 and MMP-9 were undetectable. However, untreated HebG2 cells and those treated with paclitaxel (0.1 nM) expressed mRNA specific for these markers.


CONCLUSIONS
This study suggests that: (1) increased production of NO may contribute to paclitaxel's cytotoxicity against HebG2 cells, (2) paclitaxel may inhibit tumor metastasis via inhibition of the expression of EGFR and MMPs and (3) an inverse correlation exist between NO production and expression of EGFR and MMPs.
Sayed-Ahmad
Mohamad M
MM
Department of Pharmacology, National Cancer Institute, Cairo University, Cairo.
Mohamad
Mohamad A
MA
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D009569:Nitric Oxide; D066246:ErbB Receptors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017239:Paclitaxel