Vasohibin2 promotes adriamycin resistance of breast cancer cells through regulating ABCG2 via AKT signaling pathway

Ma,Deliang; Wu,Liang; Li,Shuangjie; Sun,Zhigang; Wang,Kai

doi:10.3892/mmr.2017.7792

Vasohibin2 promotes adriamycin resistance of breast cancer cells through regulating ABCG2 via AKT signaling pathway

Authors:
- Deliang Ma
- Liang Wu
- Shuangjie Li
- Zhigang Sun
- Kai Wang
View Affiliations

Affiliations: Department of Oncology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China, Department of Breast Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Central Laboratory, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
Published online on: October 13, 2017 https://doi.org/10.3892/mmr.2017.7792
Pages: 9729-9734

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

As a well‑known angiogenic factor in different histology and pathological conditions, the pro‑progressive role of vasohibin2 (VASH2) has been reported in various types of tumors. However, its role in drug resistance of breast cancer has not been reported so far. The present study demonstrated that MCF‑7 cells with increased expression of VASH2 demonstrate stronger adriamycin (ADM) resistance compared with MDA‑MB‑231 cells with decreased expression of VASH2. Overexpression of VASH2 in MDA‑MB‑231 cells increased ADM resistance and silencing VASH2 in MCF‑7 cells inhibited ADM resistance. Furthermore, in newly established ADM resistant cell lines, VASH2 was significantly upregulated. These results revealed the promotive role of VASH2 in the ADM resistance of breast cancer cells. In addition, overexpression of VASH2 in MDA‑MB‑231 cells significantly upregulated ATP‑binding cassette sub‑family G member 2 (ABCG2), however silencing VASH2 in MCF‑7 cells inhibited ABCG2 significantly. Silencing ABCG2 abrogated increase of ADM resistance induced by VASH2 overexpression in MDA‑MB‑231 cells. This proved that VASH2 induced ADM resistance through promoting expression of ABCG2, at least in part. Further study regarding the underlying molecular mechanism demonstrated that VASH2 promoted ABCG2 via the protein kinase B (AKT) signaling pathway. Overall, VASH2 may promote drug resistance of breast cancer cells through regulating ABCG2 via the AKT signaling pathway. This suggests a novel therapeutic target to inhibit drug resistance in breast cancer, for a more efficient therapeutic outcome.

View Figures

View References

1	Clarke CA, Glaser SL, Leung R, Davidson-Allen K, Gomez SL and Keegan TH: Prevalence and characteristics of cancer patients receiving care from single vs. multiple institutions. Cancer epidemiol. 46:27–33. 2016. View Article : Google Scholar : PubMed/NCBI
2	Narayanan R and Dalton JT: Androgen receptor: A complex therapeutic target for breast cancer. Cancers (Basel). 8:pii: E1082016. View Article : Google Scholar
3	Friese CR, Li Y, Bondarenko I, Hofer TP, Ward KC, Hamilton AS, Deapen D, Kurian AW and Katz SJ: Chemotherapy decisions and patient experience with the recurrence score assay for early-stage breast cancer. Cancer. 123:43–51. 2017. View Article : Google Scholar : PubMed/NCBI
4	Cata JP, Chavez-MacGregor M, Valero V, Black W, Black DM, Goravanchi F, Ifeanyi IC, Hernandez M, Rodriguez-Restrepo A and Gottumukkala V: The impact of paravertebral block analgesia on breast cancer survival after surgery. Reg Anesth Pain Med. 41:696–703. 2016. View Article : Google Scholar : PubMed/NCBI
5	Mikkola TS, Savolainen-Peltonen H, Tuomikoski P, Hoti F, Vattulainen P, Gissler M and Ylikorkala O: Reduced risk of breast cancer mortality in women using postmenopausal hormone therapy: A Finnish nationwide comparative study. Menopause. 23:1199–1203. 2016. View Article : Google Scholar : PubMed/NCBI
6	Sato Y: The vasohibin family. Pharmaceuticals (Basel). 3:433–440. 2010. View Article : Google Scholar : PubMed/NCBI
7	Li Z, Tu M, Han B, Gu Y, Xue X, Sun J, Ge Q, Miao Y, Qian Z and Gao W: Vasohibin 2 decreases the cisplatin sensitivity of hepatocarcinoma cell line by downregulating p53. PLoS One. 9:e903582014. View Article : Google Scholar : PubMed/NCBI
8	Xue X, Zhang Y, Zhi Q, Tu M, Xu Y, Sun J, Wei J, Lu Z, Miao Y and Gao W: MiR200-upregulated Vasohibin 2 promotes the malignant transformation of tumors by inducing epithelial-mesenchymal transition in hepatocellular carcinoma. Cell Commun Signal. 12:622014. View Article : Google Scholar : PubMed/NCBI
9	Kim JC, Kim KT, Park JT, Kim HJ, Sato Y and Kim HS: Expression of vasohibin-2 in pancreatic ductal adenocarcinoma promotes tumor progression and is associated with a poor clinical outcome. Hepatogastroenterology. 62:251–256. 2015.PubMed/NCBI
10	Koyanagi T, Suzuki Y, Saga Y, Machida S, Takei Y, Fujiwara H, Suzuki M and Sato Y: In vivo delivery of siRNA targeting vasohibin-2 decreases tumor angiogenesis and suppresses tumor growth in ovarian cancer. Cancer Sci. 104:1705–1710. 2013. View Article : Google Scholar : PubMed/NCBI
11	Koyanagi T, Saga Y, Takahashi Y, Suzuki Y, Suzuki M and Sato Y: Downregulation of vasohibin-2, a novel angiogenesis regulator, suppresses tumor growth by inhibiting angiogenesis in endometrial cancer cells. Oncol Lett. 5:1058–1062. 2013.PubMed/NCBI
12	Tu M, Liu X, Han B, Ge Q, Li Z, Lu Z, Wei J, Song G, Cai B, Lv N, et al: Vasohibin-2 promotes proliferation in human breast cancer cells via upregulation of fibroblast growth factor-2 and growth/differentiation factor-15 expression. Mol Med Rep. 10:663–669. 2014. View Article : Google Scholar : PubMed/NCBI
13	Tu M, Lu C, Lv N, Wei J, Lu Z, Xi C, Chen J, Guo F, Jiang K, Li Q, et al: Vasohibin 2 promotes human luminal breast cancer angiogenesis in a non-paracrine manner via transcriptional activation of fibroblast growth factor 2. Cancer Lett. 383:272–281. 2016. View Article : Google Scholar : PubMed/NCBI
14	Takahashi Y, Koyanagi T, Suzuki Y, Saga Y, Kanomata N, Moriya T, Suzuki M and Sato Y: Vasohibin-2 expressed in human serous ovarian adenocarcinoma accelerates tumor growth by promoting angiogenesis. Mol Cancer Res. 10:1135–1146. 2012. View Article : Google Scholar : PubMed/NCBI
15	Zhao M, Yu S and Zhang M: Differential expression of multidrug resistance-related proteins in adriamycin-resistant (pumc-91/ADM) and parental (pumc-91) human bladder cancer cell lines. Mol Med Rep. 14:4741–4746. 2016. View Article : Google Scholar : PubMed/NCBI
16	Cetin I and Topcul MR: In vitro antiproliferative effects of nab-paclitaxel with liposomal cisplatin on MDA-MB-231 and MCF-7 breast cancer cell lines. J BUON. 22:347–354. 2017.PubMed/NCBI
17	Sui H, Zhou LH, Zhang YL, Huang JP, Liu X, Ji Q, Fu XL, Wen HT, Chen ZS, Deng WL, et al: Evodiamine suppresses ABCG2 mediated drug resistance by inhibiting p50/p65 NF-κB pathway in colorectal cancer. J Cell Biochem. 117:1471–1481. 2016. View Article : Google Scholar : PubMed/NCBI
18	Sun Y, Gu M, Zhu L, Liu J, Xiong Y, Wei Y and Li F: Gemcitabine upregulates ABCG2/BCRP and modulates the intracellular pharmacokinetic profiles of bioluminescence in pancreatic cancer cells. Anticancer Drugs. 27:183–191. 2016. View Article : Google Scholar : PubMed/NCBI
19	Dahlmann M, Okhrimenko A, Marcinkowski P, Osterland M, Herrmann P, Smith J, Heizmann CW, Schlag PM and Stein U: RAGE mediates S100A4-induced cell motility via MAPK/ERK and hypoxia signaling and is a prognostic biomarker for human colorectal cancer metastasis. Oncotarget. 5:3220–3233. 2014. View Article : Google Scholar : PubMed/NCBI
20	Li N, Cui J, Duan X, Chen H and Fan F: Suppression of type I collagen expression by miR-29b via PI3K, Akt, and Sp1 pathway in human Tenon's fibroblasts. Invest Ophthalmol Vis Sci. 53:1670–1678. 2012. View Article : Google Scholar : PubMed/NCBI
21	Miao B and Degterev A: Targeting phospshatidylinositol 3-kinase signaling with novel phosphatidylinositol 3,4,5-triphosphate antagonists. Autophagy. 7:650–651. 2011. View Article : Google Scholar : PubMed/NCBI
22	Hu CF, Huang YY, Wang YJ and Gao FG: Upregulation of ABCG2 via the PI3K-Akt pathway contributes to acidic microenvironment-induced cisplatin resistance in A549 and LTEP-a-2 lung cancer cells. Oncol Rep. 36:455–461. 2016. View Article : Google Scholar : PubMed/NCBI
23	He X, Wang J, Wei W, Shi M, Xin B, Zhang T and Shen X: Hypoxia regulates ABCG2 activity through the activivation of ERK1/2/HIF-1α and contributes to chemoresistance in pancreatic cancer cells. Cancer Biol Ther. 17:188–198. 2016. View Article : Google Scholar : PubMed/NCBI