Establishment of 5-Fluorouracil-resistant canine mammary tumor cell line

Abstract

Canine mammary tumors are the most common neoplasms in intact female dogs. The surgery cannot always solve the problem, chemotherapy are recommend to these patients. However, chemotherapy could always fail because of multidrug resistance (MDR). Through stepwise increasing 5-Fluorouracil (5-FU) concentration in the culture medium, a 5-FU-resistant canine mammary tumor cell line CMT7364/5-FU was established to disclose the molecular mechanism of the drug resistance. Cell morphology, cell sensitivity to drugs, growth curves, expression of proteins, and chemo-sensitivity in vivo were compared between the parental cell line and resistant cell line. As compared it to its parental cell line (CMT7364), CMT7364/5-FU showed different morphology, cross-resistant to other chemo-drugs and a prolonged population doubling time (PDT). The drug efflux pump proteins (ABCB1 and ABCG2) in CMT7364/5-FU were up-regulated. In vivo, the similar result revealed that CMT7364/5-FU cell line was more resistant to 5-FU. In conclusion, a 5-FU-resistant canine mammary tumor cell line (CMT7364/5-FU) was successfully established, it can serve as a good model for researching the mechanism of MDR and screening effective agents to reverse drug resistance.

5-Fluorouracil may enrich cancer stem cells in canine mammary tumor cells in�vitro

“…The 5-FU-resistant cell line was established from the CMT7364 cells through culturing with stepwise increasing concentrations of 5-FU (Hefei Bomei Biotechnology Co., Ltd., Anhui, China) in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) (both from Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) and antibiotics (penicillin 100 IU/ml and streptomycin 100 IU/ml; Gibco; Thermo Fisher Scientific, Inc.). The original concentration of 5-FU was 10 ng/ml, which was increased by 10 ng/ml at each interval (14 intervals total) until it reached 150 ng/ml, as previously described (14). As the concentration of 5-FU increased, the cell proliferation rate decreased.…”

Establishment and Characterization of An HER2-enriched Canine Mammary Cancerous Myoepithelial Cell Line with Stem Cell Properties

“…Similarly, CMT was subdivided based on its molecular expressions and each subtype has its own clinical signi cance that is worth studying. Over the last decade, several cell lines have been established to study CMT including CMT-7364, CMT-7367/5-FU, and B-CMT (triple negative), FR37-CMT (ER + , HER2 + ), and IPC-366 (basal-like) [29][30][31][32][33]. Nonetheless, a HER2-enriched CMT cell line has not been reported.…”