Recently, we have shown that
Hecate-CGbeta conjugate, which is a fusion of the lytic
peptide Hecate and a 15-amino
acid fragment of the beta-chain of
chorionic gonadotropin (CGbeta), selectively destroys mammary gland
carcinoma cells that possess
luteinizing hormone receptors (LHR) in vitro. We induced mammary gland
tumors using combined prenatal exposure to synthetic
diethylstilbestrol (DES) and additional postnatal exposure to dimethylbenz[a]
anthracene (DMBA). Rats with
tumors were equally randomized (10/group) and treated with either
sham (control) or 12 mg/kg body wt of either Hecate or
Hecate-CGbeta once a week for 3 weeks by tail vein
injections. One week after the last injection, rats were killed. Reverse-transcription-nested polymerase chain reaction/Southern blotting revealed alternatively spliced
mRNA for LHR in
tumor tissues of 5 of 30 females, which was further confirmed by Western blot analysis. The percentage of
tumor volume increase was lowest in the group treated with
Hecate-CGbeta (45.3 +/- 27.6), compared with Hecate- and
sham-treated, control group (324.8 +/- 78.1 and 309.9 +/- 51.2, respectively; P<0.001).
Hecate-CGbeta induced a significant decrease in
tumor burden compared with controls (9.5 +/- 2.1 mg/g body wt vs. 21.6 +/- 2.9; P<0.01). A smaller reduction in
tumor burden was also observed in Hecate-treated females (17.6 +/- 1.6 mg/g body wt vs. 21.6 +/- 2.9; P<0.05). Our results prove the principle that
Hecate-CGbeta conjugate is able to repress mammary gland
tumor growth, even in
tumor tissues that lack or have very low levels of LHR. The mechanism of
Hecate-CGbeta conjugate action in repression of DES/DMBA-induced
tumor growth needs to be further analyzed to clarify the molecular mechanisms of
Hecate-CGbeta conjugate action in vivo.