Expression of p65 gene in experimental colon cancer under the influence of 5-fluorouracil given alone and in combination with hormonal modulation.
The effect of tamoxifen (TAM), lanreotide (LAN) and 5-fluorouracil (5-FU), given separately or together, on p65 gene expression in murine Colon 38 cancer was investigated by RT-PCR method. The findings were compared with cell proliferation determined by bromodeoxyuridine (BrdU) labeling index, apoptosis visualized by TUNEL method and tumor mass. It was found that in the control group (mice bearing colon cancer without treatment) the expression of p65 gene was present in 57% of investigated samples. In the groups treated with TAM or LAN p65 gene expression was detected in 87.5% and 83.3% of analyzed cases, respectively. Both these substances increased apoptotic index in Colon 38 cancer and LAN also decreased the proliferation index. After a combined treatment with TAM and LAN a percentage of p65 positive cases was similar to that of the control group and equaled approximately 60%. This treatment did not increase proapoptotic effects of these drugs, and even reduced the antiproliferogenic effect of LAN. In the group treated with 5-FU and LAN p65 gene expression was also close to the control value (about 66%). Similarly in this group the combined treatment with these two drugs did not cause any favorable effect on proliferation and apoptosis. Moreover, in this group even reduced antiproliferogenic effect of LAN was observed. In the group with 5-FU alone the expression of p65 was present in about 80% of samples. The treatment with 5-FU increased apoptotic index and did not change proliferation. In the group treated with a combination of TAM and 5-FU all analyzed cases showed the presence of p65 gene expression. Previously, we observed in this group the most pronounced and synergistic effect of these substances on the inhibition of cell proliferation and tumor mass reduction. Based on these findings we conclude that p65 gene expression in murine Colon 38 cancer tissues can be modulated via chemotherapy (5-FU) and also via hormonal modulation (TAM and LAN).
Melen-Mucha
G
G
Department of Experimental Endocrinology and Hormone Diagnostics, Medical University of Lodz, 91-425, Poland. g.m-mucha@wp.pl
Balcerczak
E
E
Mucha
S
S
Panczyk
M
M
Lipa
S
S
Mirowski
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis*; D002455:Cell Division; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004396:Coloring Agents / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006728:Hormones / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D010456:Peptides, Cyclic / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D051996:Transcription Factor RelA
D000964:Antimetabolites, Antineoplastic; D002352:Carrier Proteins; D004396:Coloring Agents; D004965:Estrogen Antagonists; D006728:Hormones; D009363:Neoplasm Proteins; D010456:Peptides, Cyclic; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D013629:Tamoxifen; C060347:lanreotide; D013004:Somatostatin; D001973:Bromodeoxyuridine; D005472:Fluorouracil