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Effect of interleukin-7 gene transfection into ovarian carcinoma cell line SKOV3 in vitro and in vivo.

Abstract：

OBJECTIVE:To investigate the effect of interleukin-7 (IL-7) gene transfection into an established ovarian carcinoma cell line (SKOV3) in vitro and evaluate the tumorigenicity of SKOV3-IL-7 in severe combined immunodeficient (SCID) mice. METHODS:IL-7 gene was transfected into SKOV3 cells by liposome. IL-7 mRNA and protein of SKOV3-IL-7 and their parental control cells were detected by reverse transcriptive-polymerase chain reaction (RT-PCR) and Western blot, respectively. The levels of IL-7, IL-2, TNFalpha and TGFbeta1 in the supernatant were detected by ELISA. The cell cycle, HLA-ABC, HLA-DR and ICAM-1 expressions were assayed by flow cytometry. The sensitivities of tumor cells to lymphokine-activated killer (LAK) cells were measured by lactate dehydrogenase (LDH) release assay. Tumorigenicities of SKOV3-IL-7 and their parental cells in SCID mice were evaluated by macro- and histological examination, while IL-7 expression and secretion were detected by immunohistochemistry and ELISA. RESULTS:IL-7 mRNA and protein were detectable in SKOV3-IL-7 only. ICAM-1 expression was significantly higher and TGFbeta1 level in culture supernatants was significantly decreased in SKOV-IL-7, all other variables remained unchanged. The proliferative activity and cell cycle of SKOV3-IL-7 were unchanged. The cytotoxic sensitivity of SKOV3-IL-7 to LAK cells was significantly higher. Both gene-transfected and nontransfected SKOV3 cells were successfully inoculated into the peritoneal cavities of SCID mice. IL-7 proteins in plasmas and tumor tissues were detectable only in SCID mice inoculated with SKOV3-IL-7. The IL-7 engineered murine tumor models revealed better general aspects, reduced tumor development and dissemination. CONCLUSIONS:IL-7 gene transfection into SKOV3 cells downregulates TGFbeta1 secretion, upregulates ICAM-1 expression and enhances sensitivity to LAK cells in vitro. The tumorigenicity of IL-7 engineered cells in SCID mice is reduced. These findings may offer support to the development of cytokine gene therapy for ovarian carcinoma.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Xie X,Ye DF,Chen HZ,Lu WG,Fu YF,Cheng B,Zhu H

doi

10.1016/j.ygyno.2003.10.036

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

578-85

issue

eissn

0090-8258

issn

1095-6859

pii

S0090825803007200

journal_volume

pub_type

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Effect of interleukin-7 gene transfection into ovarian carcinoma cell line SKOV3 in vitro and in vivo.