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Published in: Pathology & Oncology Research 1/2020

01-01-2020 | Original Article

High Expression of PhospholipaseD2 Induced by Hypoxia Promotes Proliferation of Colon Cancer Cells through Activating NF- κ Bp65 Signaling Pathway

Authors: Maoxi Liu, Kunli Du, Bo Jiang, Xingye Wu

Published in: Pathology & Oncology Research | Issue 1/2020

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Abstract

Hypoxia is a typical feature of colon cancer occurrence and progression. We have reported that high expression and activity of PhospholipaseD2 (PLD2) induced by hypoxia in colon cancer cells. In order to further investigate the role of PLD2 in colon cancer under hypoxic conditions. MTT assay was used to detect the proliferation of human colon cancer cells (SW480 and SW620) under hypoxic conditions by decrease the PLD2 gene expression or inhibit the activity of PLD2. Expression level of p-P65/T-P65 and Cyclin D1 were detected in those cells treated as above through using western blot and RT-PCR analysis. Effect of NF-Bp65 inhibitor (BAY-117082) on the proliferation and expression level of Cyclin D1 and PLD2 of colon cancer cells under hypoxic conditions were further analysised. As a result, decreased the expression of PLD2 or inhibited the activity of PLD2 leaded to the proliferation of hypoxia colon cancer cells reduced, and along with the expression level of p-P65/T-P65 and Cyclin D1 reduced. However, inhibition the expression level of p-P65/T-P65 lead to the proliferation and expression of Cyclin D1 in those hypoxia colon cancer cells also reduced. In vivo growth decreased in response to PLD2 and NF-Bp65 inhibition. Our study indicates that high expression of PLD2 induced by hypoxia promotes the proliferation of colon cancer cells, and it may elevate the expression level of Cyclin D1 through activating NF-Bp65 signaling pathway. Inhibition of the PLD2 expression may provide a new clue for treatment for colon cancer.
Literature
1.
go back to reference Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clinic 62:10–29CrossRef Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clinic 62:10–29CrossRef
2.
go back to reference Wang Z, Sun Y (2010) Targeting P53 for novel anticancer therapy. Transl Oncol 3(1):1–12CrossRef Wang Z, Sun Y (2010) Targeting P53 for novel anticancer therapy. Transl Oncol 3(1):1–12CrossRef
3.
go back to reference Rupnarain C, Dlamini Z, Naicker S, Bhoola K (2004) Colon cancer:genomics and apoptotic events. Biol Chem 385(6):449–464CrossRef Rupnarain C, Dlamini Z, Naicker S, Bhoola K (2004) Colon cancer:genomics and apoptotic events. Biol Chem 385(6):449–464CrossRef
4.
go back to reference Uchida N, Okamura S, Kuwano H (1999) Phospholipase D activity in human gastric carcinoma. Anticancer Res 19(1B):77–86 Uchida N, Okamura S, Kuwano H (1999) Phospholipase D activity in human gastric carcinoma. Anticancer Res 19(1B):77–86
5.
go back to reference Ahn MJ, Park SY, Kim WK, Cho JH, Chang BJ, Kim DJ (2012) A single nucleotide polymorphism in the phospholipase D1 gene is associated with risk of non-small lung cancer. Int J Biomed Sci 8(2):121–128PubMedPubMedCentral Ahn MJ, Park SY, Kim WK, Cho JH, Chang BJ, Kim DJ (2012) A single nucleotide polymorphism in the phospholipase D1 gene is associated with risk of non-small lung cancer. Int J Biomed Sci 8(2):121–128PubMedPubMedCentral
6.
go back to reference Park MH, do Min S (2011) Quercetin-induced downregulation of PLD1 inhibits proliferation and invasion in U87 glioma cells. Biochem Biophys Res Commun 412(4):710–715CrossRef Park MH, do Min S (2011) Quercetin-induced downregulation of PLD1 inhibits proliferation and invasion in U87 glioma cells. Biochem Biophys Res Commun 412(4):710–715CrossRef
7.
go back to reference Toschi A, Edelstein J, Rockwell P, Ohh M, Foster DA (2008) HIF alpha expression in VHL-deficient renal cancer cells is dependent on phospholipase D. Oncogene 27(19):2746–2753CrossRef Toschi A, Edelstein J, Rockwell P, Ohh M, Foster DA (2008) HIF alpha expression in VHL-deficient renal cancer cells is dependent on phospholipase D. Oncogene 27(19):2746–2753CrossRef
8.
go back to reference Noh DY, Ahn SJ, Lee RA, Park IA, Kim JH, Suh PG, Ryu SH, Lee KH, Han JS (2000) Overexpression of phospholipase D in human breast cancer tisues. Cancer Lett 161(2):207–214CrossRef Noh DY, Ahn SJ, Lee RA, Park IA, Kim JH, Suh PG, Ryu SH, Lee KH, Han JS (2000) Overexpression of phospholipase D in human breast cancer tisues. Cancer Lett 161(2):207–214CrossRef
9.
go back to reference Oshimoto H, Okamura S, Yoshida M, Mori M (2003) Increased activity and expression of Phospholipase D2 in human colorectal cancer. Oncol Res 14(1):31–37CrossRef Oshimoto H, Okamura S, Yoshida M, Mori M (2003) Increased activity and expression of Phospholipase D2 in human colorectal cancer. Oncol Res 14(1):31–37CrossRef
10.
go back to reference Saito M, Iwadate M, Higashimoto M, Ono K (2007) Expression of phospholipase D2 in human colorectal carcinoma. Oncol Rep 18(5):1329–1334PubMed Saito M, Iwadate M, Higashimoto M, Ono K (2007) Expression of phospholipase D2 in human colorectal carcinoma. Oncol Rep 18(5):1329–1334PubMed
11.
go back to reference Yamada Y, Hamajima N, Kato T, Iwata H (2003) Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer. J Mol Med 81(2):126–131CrossRef Yamada Y, Hamajima N, Kato T, Iwata H (2003) Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer. J Mol Med 81(2):126–131CrossRef
12.
go back to reference Maoxi L, Kunli D, Zhongxue F, Shouru Z, Wu X (2015) Hypoxia-inducible factor 1-alpha up-regulates the expression of phospholipase D2 in colon cancer cells under hypoxic conditions. Med Oncol 32(1):394CrossRef Maoxi L, Kunli D, Zhongxue F, Shouru Z, Wu X (2015) Hypoxia-inducible factor 1-alpha up-regulates the expression of phospholipase D2 in colon cancer cells under hypoxic conditions. Med Oncol 32(1):394CrossRef
14.
go back to reference Liu T, Liu D, Liu J, Song JT, Gao SL, Li H, Hu LH, Lin BR (2012) Effact of NF-kappa B inhibitors on the chemotherapy-induced apoptosis of the colon cancer cell HT-29. Exp Ther Med 4(4):716–722CrossRef Liu T, Liu D, Liu J, Song JT, Gao SL, Li H, Hu LH, Lin BR (2012) Effact of NF-kappa B inhibitors on the chemotherapy-induced apoptosis of the colon cancer cell HT-29. Exp Ther Med 4(4):716–722CrossRef
15.
go back to reference Venkateswararao E, Sharma VK, Yun J, Kim Y, Jung SH (2014) Anti-proliferative effect of chalcone derivatives through inactivation of NF-κB in human cancer cell. Bioorg Med Chem 22(13):3386–3392CrossRef Venkateswararao E, Sharma VK, Yun J, Kim Y, Jung SH (2014) Anti-proliferative effect of chalcone derivatives through inactivation of NF-κB in human cancer cell. Bioorg Med Chem 22(13):3386–3392CrossRef
16.
go back to reference Kwun HJ, Lee JH, Min DS et al (2003) Transcriptional repression of cyclin-dependent kinase inhibitor p21 gene by phospholipase D1 and D2[J]. FEBS Lett 544(1–3):38–44CrossRef Kwun HJ, Lee JH, Min DS et al (2003) Transcriptional repression of cyclin-dependent kinase inhibitor p21 gene by phospholipase D1 and D2[J]. FEBS Lett 544(1–3):38–44CrossRef
17.
go back to reference Foster DA, Xu L (2003) Phospholipase D in cell proliferation and cancer. Mol Cancer Res 1(11):789–800PubMed Foster DA, Xu L (2003) Phospholipase D in cell proliferation and cancer. Mol Cancer Res 1(11):789–800PubMed
18.
go back to reference zhao Y, Ehara H, Akao Y, Shamoto M, Nakagawa Y et al (2000) Increased activity and intranyclear expression of phospholipase D2 in human renal cancer. Biochem Biophys Res Commun 278(1):140–143CrossRef zhao Y, Ehara H, Akao Y, Shamoto M, Nakagawa Y et al (2000) Increased activity and intranyclear expression of phospholipase D2 in human renal cancer. Biochem Biophys Res Commun 278(1):140–143CrossRef
19.
go back to reference Kang DW, Min DS (2109) Positive feedback regulation between phospholipase D and wnt signaling promotes wnt-driven anchorage-independent growth of colorectal cancer cells. PLoS One 5(8):2010 Kang DW, Min DS (2109) Positive feedback regulation between phospholipase D and wnt signaling promotes wnt-driven anchorage-independent growth of colorectal cancer cells. PLoS One 5(8):2010
20.
go back to reference Ye Q, Kantonen S, Gomez-Cambronero J (2012) Serum deprivation confers the MDA-MB-231breast cancer line with an EGFR/JANK3/PLD2 system that maximizes cancer cell invasion. J Mol Biol 425(4):755–766CrossRef Ye Q, Kantonen S, Gomez-Cambronero J (2012) Serum deprivation confers the MDA-MB-231breast cancer line with an EGFR/JANK3/PLD2 system that maximizes cancer cell invasion. J Mol Biol 425(4):755–766CrossRef
21.
go back to reference Bruntz RC, Taylor HE, Lindsley CW, Brown H (2014) Phospholipase D2 mediates survival signaling through direct regulation of AKT in glioblastoma cells. J Biol Chem 289(2):600–616CrossRef Bruntz RC, Taylor HE, Lindsley CW, Brown H (2014) Phospholipase D2 mediates survival signaling through direct regulation of AKT in glioblastoma cells. J Biol Chem 289(2):600–616CrossRef
22.
go back to reference Shen Q, Stanton ML, Feng W, Rodriquez ME, Ramondetta L, Chen L et al (2010) Morphoproteomic analysis reveals an overexpressed and constitutively activated phospholipase D1-m TOR pathway in endometrial carcinoma. Int J Clin Exp Pathol 4(1):13–21PubMedPubMedCentral Shen Q, Stanton ML, Feng W, Rodriquez ME, Ramondetta L, Chen L et al (2010) Morphoproteomic analysis reveals an overexpressed and constitutively activated phospholipase D1-m TOR pathway in endometrial carcinoma. Int J Clin Exp Pathol 4(1):13–21PubMedPubMedCentral
23.
go back to reference Wang Q, Zhou Y, Evers BM (2006) Pkc delta-mediated regulation of FLIP expression in human cancer cells. Int J Cancer 118:326–334CrossRef Wang Q, Zhou Y, Evers BM (2006) Pkc delta-mediated regulation of FLIP expression in human cancer cells. Int J Cancer 118:326–334CrossRef
24.
go back to reference Park MH, Ahn B-H, Hong Y-K, Min DS Overexpression of phospholipase D enhances matrix metalloproteinase-2 expression and glioma cell invasion via protein kinase C and protein kinase a/NF-κB/SP1-mdiated signaling pathways. Carcinogenesis 30(2):356–365 Park MH, Ahn B-H, Hong Y-K, Min DS Overexpression of phospholipase D enhances matrix metalloproteinase-2 expression and glioma cell invasion via protein kinase C and protein kinase a/NF-κB/SP1-mdiated signaling pathways. Carcinogenesis 30(2):356–365
25.
go back to reference Yamada M, Banno Y, Takuwa Y, Koda M, Hara A, Nozawa Y (2004) Overxpression of phospholipase D prevents actinomycin D-induced apoptosis through potentiation of phosphoinositide 3-kinase signalling pathways in Chinese-hamster ovary cells. Biochem J 378(Pt2):649–656CrossRef Yamada M, Banno Y, Takuwa Y, Koda M, Hara A, Nozawa Y (2004) Overxpression of phospholipase D prevents actinomycin D-induced apoptosis through potentiation of phosphoinositide 3-kinase signalling pathways in Chinese-hamster ovary cells. Biochem J 378(Pt2):649–656CrossRef
26.
go back to reference Oh JW, Kim EY, koo BS, Lee HB, Kim KS, Han JS Der f 2 activates phospholipase D in human T lymphocytes from Dermatophagoides farina specific allergic individuals: involvement of protein kinase C-α. Exp Mol Med 36(2004):486–492 Oh JW, Kim EY, koo BS, Lee HB, Kim KS, Han JS Der f 2 activates phospholipase D in human T lymphocytes from Dermatophagoides farina specific allergic individuals: involvement of protein kinase C-α. Exp Mol Med 36(2004):486–492
27.
go back to reference Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta DeltaC(T)) method. Methods 25:402–408CrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta DeltaC(T)) method. Methods 25:402–408CrossRef
Metadata
Title
High Expression of PhospholipaseD2 Induced by Hypoxia Promotes Proliferation of Colon Cancer Cells through Activating NF- κ Bp65 Signaling Pathway
Authors
Maoxi Liu
Kunli Du
Bo Jiang
Xingye Wu
Publication date
01-01-2020
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 1/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-018-0429-1

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