Effects of recombinant human gamma-interferon on carcinoembryonic antigen expression of human colon cancer cells.
The effects of human recombinant gamma-interferon (gamma-IFN) on the levels of carcinoembryonic antigen (CEA) expression were investigated in vitro in three human colon adenocarcinoma cell lines (WiDr, HT29, and SW403). Subconfluent cultures were exposed continuously to IFN at concentrations of 1-1,000 antiviral units/ml for up to 6 consecutive days. IFN resulted in a significant increase in CEA levels when assayed by cellular enzyme-linked immunosorbent assay (ELISA), with higher concentrations and longer exposure times resulting in greater CEA enhancement. A three to five-fold enhancement of CEA was observed after 5-6 days of continuous exposures at concentrations of 100-1,000 antiviral units/ml. CEA levels returned to baseline over a 4-day period after discontinuation of IFN. Levels of IFN that resulted in CEA enhancement also resulted in cell growth inhibition, with a direct correlation observed. Flow cytometric studies, which evaluated changes in CEA membrane expression of only the viable cells remaining after IFN exposure, gave similar results to cellular ELISA. Quantitative CEA ELISA, which quantitated changes in total cellular CEA content, demonstrated greater increase in CEA than predicted by cellular ELISA. Continuous IFN exposures for 5-6 days at 1,000 U/ml led to a 96-, 26-, and 5-fold increase in total CEA for the WiDr, HT29, and SW403 cell lines, respectively. WiDr cells exposed to daily 6-h IFN pulses demonstrated intermediate increases in CEA compared with cells exposed continuously to IFN.(ABSTRACT TRUNCATED AT 250 WORDS)
Yan
X W
XW
Division of Radiation Oncology, City of Hope National Medical Center, Duarte, California 91010.
Wong
J Y
JY
Esteban
J M
JM
Kuhn
J A
JA
Beatty
B G
BG
Beatty
J D
JD
Shively
J E
JE
D000230:Adenocarcinoma / Q000737:chemistry / Q000188:drug therapy*; D002272:Carcinoembryonic Antigen / Q000032:analysis*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005069:Evaluation Studies as Topic; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016499:Radioimmunotherapy; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D011994:Recombinant Proteins; D007371:Interferon-gamma