Pancreatic cancer is one of the most lethal human cancers and continues to be a major unsolved health problem. The overexpression of the epidermal growth factor receptor and its ligands correlates with rapidly progressive disease and resistance to chemotherapy.
This study investigated the growth inhibitory effects of erlotinib in pancreatic cancer cells in vitro and in vivo.
Many gastrointestinal tumors, including pancreatic cancer, have been shown to overexpress the EGFR. The overexpression of EGFR correlates with rapidly progressive disease and poor prognosis. Targeting EGFR pathway as a potential therapeutic strategy for pancreatic cancer has been developed. Erlotinib is a small molecule tyrosine kinase inhibitor that efficiently blocks EGFR. Preliminary results of phase III trial in pancreatic cancer revealed an improvement in survival with the addition of erlotinib. Treatment with anti-EGFR agents is used as a potential therapeutic strategy for pancreatic cancer, but the mechanisms are not yet precisely understood.
The research team from Department of Gastroenterology, Affiliated First People's Hospital, Shanghai Jiao Tong University, China studied the effects of erlotinib on six different pancreatic cancer cell lines. How erlotinib exhibits its antineoplastic activity in vivo needs to be further elucidated.
In this study authors revealed the efficacy of erlotinib, as a single agent, on pancreatic cancer cells growth in vitro, and in vivo study using a nude mice xenograft model and the mechanisms involved were also explored. Erlotinib repressed BxPC-3 cell growth in a dose-dependent manner, triggered G1 arrest and induced cell apoptosis,and suppressed capillary formation of endothelium in vitro.
In vivo, erlotinib treated mice demonstrated a reduced tumor volume and weight as compared with control. The relationship between EGFR and angiogenesis has also been investigated using tube formation assay in vitro and immunohistochemical analysis of tumor-associated blood vessels in vivo. These findings provide evidence for the inhibitive activity of erlotinib in pancreatic cancer cells. Inhibition of EGFR may be a promising adjuvant in chemotherapeutic strategy in the treatment of the dismal disease. The results also demonstrate that EGFR signaling pathway is an important target in pancreatic cancer.
- Lu et al. Anti-tumor activity of erlotinib in the BxPC-3 pancreatic cancer cell line. World Journal of Gastroenterology, September 21, 2008; 14 (35): 5403 DOI: 10.3748/wjg.14.5403
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