Reference

AKT inhibition is associated with chemosensitization in the pancreatic cancer cell line MIA-PaCa-2

AKT inhibition is associated with chemosensitization in the pancreatic cancer cell line MIA-PaCa-2. Fahy, B. N.; Schlieman, M.; Virudachalam, S.; Bold, R.Some commonly used reagents like 115926-52-8 and 95058-81-4 are used in this experiment. J. (Department of Surgical Oncology, University of California Davis Cancer Center, Sacramento, CA 95817, USA). British Journal of Cancer, 89(2), 391-397 (English) 2003 Nature Publishing Group. CODEN: BJCAAI. ISSN: 0007-0920. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Activation of the serine/threonine kinase AKT is common in pancreatic cancer; inhibition of which sensitizes cells to the apoptotic effect of chemotherapy. Of the various downstream targets of AKT, we examd. activation of the NF-kB transcription factor and subsequent transcriptional regulation of BCL-2 gene family in pancreatic cancer cells. Inhibition of either phosphatidylinositol-3 kinase or AKT led to a decreased protein level of the antiapoptotic gene BCL-2 and an increased protein level of the proapoptotic gene BAX. Furthermore, inhibition of AKT decreased the function of NF-kB, which is capable of transcriptional regulation of the BCL-2 gene. Inhibiting this pathway had little effect on the basal level of apoptosis in pancreatic cancer cells, but increased the apoptotic effect of chemotherapy. The antiapoptotic effect of AKT activation in pancreatic cancer cells may involve transcriptional induction of a profile of BCL-2 proteins that confer resistance to apoptosis; alteration of this balance allows sensitization to the apoptotic effect of chemotherapy. .

Adenovirus Type 5 E1A Sensitizes Hepatocellular Carcinoma Cells to Gemcitabine

Some chemicals with cas registry numbers like 9055-67-8 and 95058-81-4 are also used. Adenovirus Type 5 E1A Sensitizes Hepatocellular Carcinoma Cells to Gemcitabine. Lee, Wei-Ping; Tai, Dar-In; Tsai, Sun-Lung; Yeh, Chau-Ting; Chao, Yee; Lee, Shou-Dong; Hung, Mien-Chie (Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan). Cancer Research, 63(19), 6229-6236 (English) 2003 American Association for Cancer Research. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy. A few clin. trials have shown that the cytidine analog gemcitabine appears to have antitumor activity for HCC, but the overall survival times remain to be improved. In this study, we examd. the synergistic effect of adenovirus type 5 E1A (E1A) and gemcitabine on HCC and found that E1A sensitized J5, J7, Huh7, and HepG2 HCC cells to gemcitabine. To further study the E1A-mediated chemosensitization, we established stable cell lines that expressed the E1A gene and then examd. whether E1A could have proapoptotic activity while expressed in HCC cells. Our results clearly showed that E1A sensitized HCC cells to gemcitabine through induction of apoptosis. To study the underlying mechanism, we tested nuclear factor (NF)-kB activity and found that NF-kB was activated in HCC cells treated with gemcitabine but not in HCC cells that expressed E1A. Occurrence of apoptosis entails cleavage of poly (ADP-ribose) polymerase (PARP), a nuclear protein involved in DNA repair, genome stability, and maintenance of telomere length. Our study showed that gemcitabine enhanced PARP expression. However, E1A did not induce PARP cleavage but rather suppressed PARP expression at the transcriptional level. Further study showed that both NF-kB and PARP played protective roles in the prevention of E1A+gemcitabine-induced apoptosis. .