Medroxyprogesterone acetate inhibits human pancreatic carcinoma cell growth by inducing apoptosis in association with Bcl-2 phosphorylation.

BACKGROUND

A previous study found that medroxyprogesterone acetate (MPA) delayed the in vivo growth of three (AsPC-1, Capan-2, and MiaPaCa-2) of nine human pancreatic carcinoma cell lines transplanted into nude mice (Cancer 1995; 75:1263-72). The current study was undertaken to evaluate the basis for this inhibitor.

METHODS

The estrogen receptor (ER) and progesterone receptor (PgR) status in nine human pancreatic carcinoma cell lines, AsPC-1, BxPC-3, Capan-1, Capan-2, Hs-700T, Hs-766T, MiaPaCa-2, PANC-1, and SUIT-2, was assessed using an enzyme immunoassay (EIA). The authors tested the growth inhibitory activity of MPA and the morphologic changes in these nine pancreatic carcinoma cell lines. Cell cycle progression and DNA fragmentation also were evaluated in these cell lines. Immunoblot analysis was used to determine bcl-2 expression and phosphorylation.

RESULTS

In the EIA assay, ER was detected in three cell lines (BxPC-3, Capan-2, and MiaPaCa-2), and PgR was also detected in three (AsPC-1, Capan-2, and MiaPaCa-2). Medroxyprogesterone acetate inhibited the growth of three cell lines (AsPC-1, Capan-2, and MiaPaCa-2) with IC50 values ranging from 2.3 x 10(7) to 6.1 x 10(-7) M. In these three responsive cell lines, MPA caused cell detachment and decreased cell density. The nuclei of the MPA-treated cells were condensed and often fragmented. Cell cycle analysis of these three cell lines showed that MPA induced the appearance of a sub-G1 peak, which is characteristic of early apoptotic cells. DNA degradation assay after MPA treatment showed a typical DNA ladder pattern consistent with apoptosis. Immunoblot analysis of MPA-treated cells that overexpressed bcl-2 revealed a pattern consistent with bcl-2 phosphorylation.

CONCLUSIONS

Clinically attainable concentrations of MPA can inhibit the growth of some human pancreatic carcinoma cells in vitro by inducing apoptosis, probably through their PgR, in association with the phosphorylation of bcl-2. This agent may be useful for treating patients with pancreatic carcinoma.