Anti-proliferative effect of retinoids and interferon-α-2a on vaginal cell lines derived from squamous intra-epithelial lesions
✍ Scribed by Sakari Hietanen; Eeva Auvinen; Kari Syrjänen; Stina Syrjänen
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 185 KB
- Volume
- 78
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
A panel of retinoids (all-trans-, 13-cis-, 19-cis retinoic acid and acitretin), and interferon-␣-2a was tested for the capacity to modulate the proliferation of UT-DEC-1 (HPV-33-positive) and UT-DEC-2 (HPV-16-positive) cell lines derived from vaginal intra-epithelial neoplasias (VAIN). At concentrations 10 ؊6 to 10 ؊8 M, all retinoids inhibited the growth of earlypassage UT-DEC cell lines, but also of normal vaginal keratinocytes and fibroblasts. The inhibition was significantly reduced in late-passage UT-DEC cells. The effect on proliferation was essentially equal for all retinoids in high (1.8 mM)-Ca 2؉ medium, but decreased markedly in low (0.09 mM)-Ca 2؉ medium. Interferon-␣-2a at 1000 IU/ml had an additive growth-inhibitory effect in the low-and in the high-Ca 2؉ medium. No consistent decrease in HPV E6-E7 mRNA levels could be associated either with retinoid or with interferon effect in either cell line. The expression of TGF1 and TGF2 mRNA increased 2-to 3-fold by 10 ؊6 M 13-cis-RA treatment in early-and in late-passage cells of both cell lines. TGF1 at 0.1 to 1.0 ng/ml also inhibited the proliferation of both cell lines, and was more effective at early passage, but the inhibition was not dependent on calcium concentration. Neutralizing anti-TGF antibodies partially relieved the proliferation inhibition by 13-cis-RA. The results show that the calciumassociated regulation of growth by the tested retinoids was seen in normal vaginal cells and in early pre-neoplastic cells, but was significantly reduced in cells with higher-grade phenotype, while also suggesting that the loss of responsiveness to retinoids and TGF may play a role in the progression of squamous intra-epithelial neoplasia.