Hsp70 response to 5-fluorouracil treatment in human colon cancer cell lines.
OBJECTIVE
Colorectal cancer is a common disease with high rate of mortality. Although there is evidence of some benefits of 5-fluorouracil (5-FU), the most commonly used drug in colon cancer therapy, it still remains unsatisfactory because of intrinsic or acquired drug resistance. Heat shock proteins (Hsps) synthesis can be increased by cellular insults, such as chemotherapy-induced damage. Inducible Hsp70 has been suggested to be involved in cytoprotection against apoptosis. In the present study, we investigated whether the content of Hsp70 is associated to 5-FU resistance.


METHODS
HT-29 and SNU-C4 human colon cancer cell lines were treated with 5-FU and their relative chemoresistance, and Hsp70 were determined.


RESULTS
Comparison of IC(50) values showed that the HT-29 cells were relatively resistant to 5-FU, whereas the SNU-C4 cells presented greater sensitivity to this drug. Further, 5-FU treatment leads to a hypodiploid population in HT-29 cells significantly lower compared to SNU-C4 cells. In the HT-29 cell line, 5-FU treatment promoted an increase of 5.5 times in Hsp70 concentration after 12 h. Then, within 24 h, the increase in Hsp70 levels was still about two times. In contrast, in the SNU-C4 cell line, 5-FU induced an increase of about two times in the Hsp70 content after 12 h and, after 24 h, did not significantly affect Hsp70 content.


CONCLUSIONS
These data suggest that 5-FU induced Hsp70 synthesis in the HT-29 resistant cell line and that this Hsp70 accumulation could protect against 5-FU-induced apoptosis. Thus, Hsp70 protection against 5-FU-induced apoptosis might underlie colon cancer chemoresistance.
Grivicich
Ivana
I
Laboratório de Marcadores de Estresse Celular, Centro de Pesquisas em Ciências Médicas, Universidade Luterana do Brasil, Canoas, Rio Grande do Sul, Brazil. grivicich@terra.com.br
Regner
Andréa
A
Zanoni
Caroline
C
Correa
Larissa Procópio
LP
Jotz
Geraldo Pereira
GP
Henriques
João Antônio Pêgas
JA
Schwartsmann
Gilberto
G
da Rocha
Adriana Brondani
AB
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D013997:Time Factors
D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D005472:Fluorouracil