J Korean Cancer Assoc.  1997 Aug;29(4):555-564.

Effects of Interleukin-2 Transduction into the Human Hepatoma Cell Lines Using Retroviral Vector

Affiliations
  • 1Department of Internal Medicine, Yonsei University, College of Medicine, Seoul, Korea.
  • 2Department of General Surgery, Yonsei University, College of Medicine, Seoul, Korea.
  • 3Department of Pathology, Yonsei University, College of Medicine, Seoul, Korea.
  • 4Yonsei Cancer Center, Yonsei University, College of Medicine, Seoul, Korea.
  • 5Yonsei Institute for Cancer Research, Yonsei University, College of Medicine, Seoul, Korea.

Abstract

PURPOSE: We compared the differences between parent hepatoma cell lines and interleukin-2 (IL-2) transduced hepatoma cell lines using N2A/IL-2 and LNC/IL-2 retrovirus with regards to in vitro sensitivity to peripheral blood monocytes and in vivo tumorigenic activity.
MATERIALS AND METHODS
Retroviral vector and producer cell line were constructed and IL-2 gene was transduced into the human hepatoma cell lines (SK-Hep1, Hep-G2, Hep-3B). IL-2 secretion after IL-2 transduction was measured by ELISA. MTT assay for in vitro sensitivity to peripheral blood monocytes was performed and the tumorigenic activity was observed in BALB/c mice and nude mice.
RESULTS
IL-2 secretion was 186 pg/10 degrees C cells/24 hrs in SK-Hep1 cell line and was 147 pg/10 (6) cells/24 hrs in Hep-3B cell line with N2A/IL-2 retroviral vector and was 55,000 pg/10 (6) cells/24 hrs with LNC/IL-2 retroviral vector. In vitro sensitivity to peripheral blood monocytes was increased by 163.8~254% in IL-2 transduced hepatoma cell lines (Hep -3B/N2A/IL-2, Hep-G2/N2A/IL-2) compared to those of the parent cell lines. The tumorigenicity was observed in 1 of 3 BALB/c mice and all 3 nude mice. Simultaneous injection of 1 X 10 (7) cells of the parent cell line (Hep-3B) into the right flank and IL-2 transduced cell line (Hep-3B/LNC/IL-2) into the left flank of the three BALB/c mice and of 5 X 10 (5) cells for the three nude mice resulted in a complete regression of the IL-2 modified tumor cell line (Hep-3B/LNC/IL-2) in 3 weeks and the parent cell line (Hep-3B) in 5 weeks. But, after the injection of 1.5 X 10 (7) cells for other five nude mice, the tumor of the IL-2 transduced hepatoma cell line (Hep-3B/LNC/IL-2) was gradually disappeared, and the tumor of the parent hepatoma cell line (Hep-3B) was initially decreased and then gradually regrew 20 days later.
CONCLUSION
IL-2 transduced hepatoma cell lines secreting IL-2 became more sensitive to peripheral blood monocytes and resulted in the increased antigenicity to the tumors formed by IL-2 transduced hepatoma cell line and parent cell line, and finally resulted in the regression of the tumors in experimental animals.

Keyword

Interleukin-2; Hepatoma cell line; Tumor regression

MeSH Terms

Animals
Carcinoma, Hepatocellular*
Cell Line*
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Humans*
Interleukin-2*
Mice
Mice, Nude
Monocytes
Parents
Retroviridae
Zidovudine*
Interleukin-2
Zidovudine
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