Collectively, we hypothesized that ritonavir might enhance the antitumor activity of docetaxel, the latter being a substrate for CYPA. In this study, we found that ritonavir, saquinavir, and indinavir inhibited the growth of the DU and PC AIPC cells as measured by the clonogenic assay.Ritonavir blocked the docetaxelinduced expression of CYPA at the mRNA level in DU cells and enhanced the antitumor effect of docetaxel in vitro and in BNX nude mice bearing DU tumors.One of the promising chemotherapeutic treatments for individuals with AIPC is docetaxel, which has antiprostate cancer effects in of individuals with AIPC have become important tools in the management of HIV infection; these include Revefenacin saquinavir mesylate, ritonavir, and indinavir sulfate.The costs of publication of this article were defrayed in part by the payment of page charges.Docetaxel was dissolved in PBS to a stock concentration of molL and stored at C.The feeder layer was prepared with agar that had been equilibrated at C.DU cells and ritonavir either alone or in combination for hours in sixwell plates.Lysates were made by standard methods as described previously. The band intensities were measured using densitometry.Colonies were enumerated after days of incubation.Results are expressed as a mean percentage of control plates containing. Results are expressed as a mean percentage of control plates containing. DU cells were cultured with docetaxel, or the combination of both for days.Briefly, nuclear extracts were prepared as described previously and incubated in well plates coated with immobilized oligonucleotide binding site for the p subunit of NFB.Background binding was subtracted from the value obtained for binding to the consensus DNA sequence.Ritonavir was administered intravenously once a week.The dose of ritonavir and docetaxel was determined by our preliminary studies.Tumors were measured every week with vernier calipers.Tumor size was calculated by the formula: a b c, where a is the length and b is the width and c is the height in millimeters.At the end of the experiment, animals were sacrificed by CO asphyxiation, and tumor weights were measured after their careful resection.Blood also was collected from the orbital sinus for chemistry and hematopoietic analysis.Results represent the mean SD of two experiments done in duplicate.Cold competition was performed using either wildtype NFB DNA binding oligonucleotides. DU cells were transiently transfected with either NFB siRNA or nonspecific siRNA.The blots were developed using the enhanced chemiluminescence kit.On the third day of culture, the cell numbers and viability were evaluated by MTT assay.Doseresponse curves were drawn, and the ED that inhibited colony formation was determined.The most effective PI was ritonavir, which caused a decrease clonal growth of DU cells at molL. Ritonavir and saquinavir showed nearly equivalent potency against PC cells with an ED of molL in soft agar containing cytokines including interleukin and granulocyte macrophagecolony stimulating factor even at a high concentration of PI. The cleavage of PARP is thought to be a late event in apoptosis.For example, the activated form of caspase and cleaved PARP were negligible in DU cells treated with docetaxel induced activation of caspase and cleavage of PARP in DU cells.

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