【Abstract】Objective to explore the possible role of erlotinib in the treatment of pancreatic cancer. Methods Methods were used to detect and analyze the growth inhibitory dose of erlotinib and its effect on the growth factor activity of pancreatic cancer cell lines. Western blot analysis was used to observe the expression levels of each member of the receptor family in pancreatic cancer cell lines. Soft agar assay was used to detect cell colony formation. Results Erlotinib inhibited cell proliferation of pancreatic cancer cell lines at concentrations ranging from to to >. Erlotinib can completely inhibit epidermal growth factor ([]
)-induced cell proliferation. Conclusion Erlotinib inhibits the growth of pancreatic cancer cells through an epidermal growth factor receptor-dependent pathway, which indicates that erlotinib provides a possible new method for the treatment of pancreatic cancer.
Many growth factor receptors and their ligands are highly expressed in pancreatic cancer, and they affect tumor growth and differentiation, invasion, metastasis and angiogenesis. Experimental studies in vitro and in vivo have shown that activation is involved in the regulation of several cellular functions that play an important role in cell transformation and tumor pathology, including proliferation and differentiation, metastasis, induction of angiogenesis, and resistance to chemotherapy and radiotherapy []. Based on these data, it was shown that epidermal growth factor receptor may be a new target for the treatment of human cancer. Erlotinib is a type I human epidermal growth factor tyrosine kinase inhibitor. It competes with adenosine triphosphate to bind to the catalytic part of the intracellular domain of the receptor tyrosine kinase in cells, inhibiting the phosphorylation reaction and thereby preventing the downstream cell signal transduction.
In vitro experimental studies have shown that it inhibits the growth of lung cancer and colorectal cancer cells. Belongs to the tyrosine kinase receptor family. This receptor family includes four members, which are often overexpressed in pancreatic cancer cells. In vitro experiments on human pancreatic cancer cells showed that , and amphiregulin significantly enhanced the proliferation of these cells [ ]. Therefore, the overexpression of the receptor family in pancreatic cancer cells suggests that autocrine and/or paracrine mechanisms play an important role in the pathogenesis of pancreatic cancer cell growth. The coexistence of its ligands/is associated with enhanced tumor invasion, shorter survival time after tumor resection [ ], and tumor prognosis [ ].
Erlotinib is a selective small molecule that can block signaling pathways involved in tumor cell proliferation and growth. Experiments have proven that erlotinib not only reduces cell proliferation but also induces the cell cycle to enter the stasis phase, accelerates cell apoptosis, and has anti-angiogenic effects []. We have concluded from experiments that concentration-dependent erlotinib has different LD50 in inhibiting the growth of pancreatic cancer cells. The value of LD50 is partially consistent with the expression of , which indicates that erlotinib exerts its inhibitory effect through targeting. However, by expressing lower levels of LD50 values achieved, it is possible that it may act on targets other than Erlotinib has a synergistic effect in combination with chemotherapy, and a relatively high frequency of clinical responses has been observed in patients with non-small cell lung cancer, which may be due to the blocking of signaling pathways by erlotinib. Therefore, we infer that erlotinib exerts its effect mainly through pathways in pancreatic cancer, but the possibility of other targets and signaling pathways cannot be ruled out. Our experiments showed that low concentrations of erlotinib weakened the clonogenic potency of pancreatic cancer cells. Because anchorage-independent growth and cell invasion are signs of increased biological toxicity of tumor cells, erlotinib's ability to block these two behaviors suggests that it may be a good drug to inhibit tumor spread and transformation. drug.
In summary, although the LD50 in pancreatic cancer cells is relatively high compared with the level of erlotinib in patient plasma, low concentrations of erlotinib can significantly inhibit pancreatic cancer. Cell lineage cell invasion and clonogenesis. Considering the poor prognosis of pancreatic cancer and the high frequency of overexpression of family receptors and ligands, erlotinib provides a promising new agent for the treatment of pancreatic cancer due to its remarkable kinetic mechanism.
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