Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]

Publication Date:
2018-08-11
Publisher:
The American Society for Pharmacology and Experimental Therapeutics
Print ISSN:
0022-3565
Electronic ISSN:
1521-0103
Topics:
Medicine
Published by:
http://www.aspet.org/
_version_ 1836399026759532544
autor Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
beschreibung Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiation therapy (RT)-mediated anticancer effects has not yet been explored. We investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assays, we found that RT-induced proliferative inhibition was critically associated with SET expression. We next tested a novel SET antagonist, N 4 -(3-ethynylphenyl)-6,7-dimethoxy-N 2 -(4-phenoxyphenyl) quinazoline-2,4-diamine (EMQA), in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared with mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore protein phosphatase 2A-mediated phospho-Akt (p-AKT) downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach.
citation_standardnr 6318224
datenlieferant ipn_articles
feed_id 1930
feed_publisher The American Society for Pharmacology and Experimental Therapeutics
feed_publisher_url http://www.aspet.org/
insertion_date 2018-08-11
journaleissn 1521-0103
journalissn 0022-3565
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Society for Pharmacology and Experimental Therapeutics
quelle Journal of Pharmacology and Experimental Therapeutics
relation http://jpet.aspetjournals.org/cgi/content/short/366/3/410?rss=1
search_space articles
shingle_author_1 Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
shingle_author_2 Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
shingle_author_3 Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
shingle_author_4 Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
shingle_catch_all_1 Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiation therapy (RT)-mediated anticancer effects has not yet been explored. We investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assays, we found that RT-induced proliferative inhibition was critically associated with SET expression. We next tested a novel SET antagonist, N 4 -(3-ethynylphenyl)-6,7-dimethoxy-N 2 -(4-phenoxyphenyl) quinazoline-2,4-diamine (EMQA), in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared with mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore protein phosphatase 2A-mediated phospho-Akt (p-AKT) downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach.
Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
The American Society for Pharmacology and Experimental Therapeutics
0022-3565
00223565
1521-0103
15210103
shingle_catch_all_2 Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiation therapy (RT)-mediated anticancer effects has not yet been explored. We investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assays, we found that RT-induced proliferative inhibition was critically associated with SET expression. We next tested a novel SET antagonist, N 4 -(3-ethynylphenyl)-6,7-dimethoxy-N 2 -(4-phenoxyphenyl) quinazoline-2,4-diamine (EMQA), in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared with mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore protein phosphatase 2A-mediated phospho-Akt (p-AKT) downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach.
Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
The American Society for Pharmacology and Experimental Therapeutics
0022-3565
00223565
1521-0103
15210103
shingle_catch_all_3 Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiation therapy (RT)-mediated anticancer effects has not yet been explored. We investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assays, we found that RT-induced proliferative inhibition was critically associated with SET expression. We next tested a novel SET antagonist, N 4 -(3-ethynylphenyl)-6,7-dimethoxy-N 2 -(4-phenoxyphenyl) quinazoline-2,4-diamine (EMQA), in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared with mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore protein phosphatase 2A-mediated phospho-Akt (p-AKT) downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach.
Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
The American Society for Pharmacology and Experimental Therapeutics
0022-3565
00223565
1521-0103
15210103
shingle_catch_all_4 Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiation therapy (RT)-mediated anticancer effects has not yet been explored. We investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assays, we found that RT-induced proliferative inhibition was critically associated with SET expression. We next tested a novel SET antagonist, N 4 -(3-ethynylphenyl)-6,7-dimethoxy-N 2 -(4-phenoxyphenyl) quinazoline-2,4-diamine (EMQA), in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared with mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore protein phosphatase 2A-mediated phospho-Akt (p-AKT) downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach.
Huang, C.-Y., Hung, M.-H., Shih, C.-T., Hsieh, F.-S., Kuo, C.-W., Tsai, M.-H., Chang, S.-S., Hsiao, Y.-J., Chen, L.-J., Chao, T.-I., Chen, K.-F.
The American Society for Pharmacology and Experimental Therapeutics
0022-3565
00223565
1521-0103
15210103
shingle_title_1 Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
shingle_title_2 Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
shingle_title_3 Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
shingle_title_4 Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
timestamp 2025-06-30T23:36:26.438Z
titel Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
titel_suche Antagonizing SET Augments the Effects of Radiation Therapy in Hepatocellular Carcinoma through Reactivation of PP2A-Mediated Akt Downregulation [Chemotherapy, Antibiotics, and Gene Therapy]
topic WW-YZ
uid ipn_articles_6318224