Growth factor receptors with tyrosine kinase activity mediate paracrine and autocrine growth regulation of normal and malignant cells. The epidermal growth factor receptor (EGF-R) is a tyrosine kinase transmembrane protein that is overexpressed by many epithelial malignancies[1]. RG13022, a tyrosine kinase inhibitor, inhibits the autophosphorylation reaction of the EGF-R in immunoprecipitates with an IC50 of 4 μM. RG-13022 inhibits DNA synthesis and colony formation by HER 14 cells, which are stimulated by 50 ng/mL EGF, in a dose-dependent manner. The IC50s for RG-13022 are 3 μM and 1 μM for HER 14 DNA synthesis and HER 14 colony formation, respectively. RG-13022 also suppresses DNA synthesis and colony formation by EGF-stimulated MH-85 cells in a dose-dependent manner. The IC50s for RG-13022 on MH-85 cells are 1.5 μM and 7 μM for DNA synthesis and colony formation, respectively. Nude mice implanted with MH-85 tumors manifested profound hypercalcemia, cachexia, and leukocytosis as the tumor grew. RG-13022 (400 μg/mouse/day) significantly inhibits MH-85 tumor growth in Nude Mice. Because of slower tumor growth, MH-85 tumor-bearing animals receiving injections of RG-13022 show less cachexia and hypercalcemia, eat more food, and are more active than untreated MH-85 tumor-bearing animals. RG-13022 prolongs the life span of MH-85 tumor-bearing animals as a result of suppression of tumor growth. Moreover, administration of mAb108 i.p. (1 mg/mouse/day) at 1, 5, and 10 days after MH-85 inoculation of RG-13022 (400 μg/mouse/day) for 14 days profoundly inhibits MH-85 growth in nude mice[2].
RG13022 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HN5 cells
0.1-100 µM
48 hours
Evaluate the inhibitory effect of RG13022 and its geometric isomer on DNA synthesis and cytotoxicity in HN5 cells. RG13022 inhibited DNA synthesis with an IC50 of 11.0 μM, while the geometric isomer had an IC50 of 38.0 μM. Neither showed significant cytotoxicity at 100 μM.
Br J Cancer. 1996 Dec;74(11):1714-8
RG13022 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
MFI nu/nu mice
HN5 tumor xenograft model
Intraperitoneal injection
400 μg/day
Once daily for 21 days
Assess the anti-tumor effect of RG13022 on HN5 tumor xenografts. RG13022 did not significantly inhibit tumor growth when administered starting on the day of tumor inoculation or after tumors reached 50 mm3.
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