Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 11, November, p. 1337–1345

doi: 10.17219/acem/127681

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Paclitaxel inhibits proliferation and invasion and promotes apoptosis of breast cancer cells by blocking activation of the PI3K/AKT signaling pathway

Gang Li1,A,B,C,D, Dongxin Xu2,A,B,C,D, Jinju Sun3,C,D, Shiyun Zhao4,A,C,D, Dan Zheng5,E,F

1 First Department of Oncology Surgery, Hangzhou Cancer Hospital, China

2 Fourth Department of Internal Medicine, Zibo City Traditional Chinese Medicine Hospital, China

3 Department of Pharmacy, The Second People’s Hospital of Liaocheng, China

4 Disinfection Supply Center, Maternal and Child Health Care of Zaozhuang, China

5 Department of Pharmacy, Hangzhou Cancer Hospital, China


Background. Breast cancer has the highest incidence and mortality among all cancers in women. Paclitaxel (PTX) has a notable therapeutic effect on cancer in clinical practice.
Objectives. To explore the effect and mechanism of PTX on the proliferation, apoptosis and invasiveness of breast cancer cells.
Material and Methods. MCF-7 cells were treated with PTX (0 μM, 0.01 μM, 0.1 μM, 1 μM) for 48 h. Cell viability was detected using MTT assay and lactate dehydrogenase (LDH) assay; the cell proliferation rate was detected using 5-ethynyl-2’-deoxyuridine (EdU) assay to screen the most effective concentration of PTX. MCF-7 cells were then divided into 5 groups: control group, PTX group, oe-PI3K group, NC-PI3K group, and oe-PI3K+PTX group. Cell apoptosis and cell cycles were detected with flow cytometry; cell invasion was determined using a transwell assay; western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to measure the mRNA and protein expression level of cleaved caspase-3, Bax, Bcl-2, matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), p-AKT (Thr308), and p-AKT (Ser473).
Results. Paclitaxel inhibited cell viability and proliferation in a dose-dependent manner. In the PTX group, the apoptosis rate, the number of cells arrested in the G2/M phase and the expression levels of Cleaved caspase-3 and Bax were increased, but the number of invasive cells and the expression levels of Bcl-2, MMP-9, vascular endothelial growth factor (VEGF), p-AKT (Thr308), and p-AKT (Ser473) were decreased. However, PI3K upregulation can reverse the effects of PTX.
Conclusion. Paclitaxel could inhibit MCF-7 cell proliferation and invasion, and promote MCF-7 cell apoptosis by downregulating the expression of p-AKT (Thr308) and p-AKT (Ser473) in the PI3K/AKT signaling pathway.

Key words

apoptosis, breast cancer, proliferation, paclitaxel, PI3K/AKt signaling pathway

References (38)

  1. Shamsi M, Pirayesh Islamian J. Breast cancer: Early diagnosis and effective treatment by drug delivery tracing. Nucl Med Rev Centr East Eur. 2017;20(1):45–48.
  2. Zhang Y, Li H, Zhang J, et al. The combinatory effects of natural products and chemotherapy drugs and their mechanisms in breast cancer treatment. Phytochem Rev. 2019;19(6):1179–1197.
  3. Shawky MS, Huo CW, Henderson MA, Redfern A, Britt K, Thompson EW. A review of the influence of mammographic density on breast cancer clinical and pathological phenotype. Breast Cancer Res Treat. 2019;177(2):251–276.
  4. Miles RC, Lehman CD, Mercaldo SF, Tamimi RM, Dontchos BN, Narayan AK. Obesity and breast cancer screening: Cross-sectional survey results from the behavioral risk factor surveillance system. Cancer. 2019;125(23):4158–4163.
  5. Jones ME, Schoemaker MJ, Wright LB, Ashworth A, Swerdlow AJ. Smoking and risk of breast cancer in the Generations Study cohort. Breast Cancer Res. 2017;19(1):118.
  6. Wong G, Au E, Badve SV, Lim WH. Breast cancer and transplantation. Am J Transplant. 2017;17(9):2243–2253.
  7. Arpino G, Milano M, De Placido S. Features of aggressive breast cancer. Breast. 2015;24(5):594–600.
  8. Jia Y, Weng Z, Wang C, et al. Increased chemosensitivity and radiosensitivity of human breast cancer cell lines treated with novel functionalized single-walled carbon nanotubes. Oncol Lett. 2017;13(1):206–214.
  9. Lue X, Deng Q, Li H, Suo Z. Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy. Exp Ther Med. 2011;2(5):821–826.
  10. Kantor O, Bao J, Jaskowiak N, Yao K, Tseng J. The prognostic value of the AJCC 8th Edition Staging System for patients undergoing neoadjuvant chemotherapy for breast cancer. Ann Surg Oncol. 2020;27(2):352–358.
  11. Bressand D, Novell A, Girault A, et al. Enhancing Nab-paclitaxel delivery using microbubble-assisted ultrasound in a pancreatic cancer model. Mol Pharm. 2019;16(9):3814–3822.
  12. Leung JC, Cassimeris L. Reorganization of paclitaxel-stabilized microtubule arrays at mitotic entry: Roles of depolymerizing kinesins and severing proteins. Cancer Biol Ther. 2019;20(10):1337–1347.
  13. Ma X, Özliseli E, Zhang Y, Pan G, Wang D, Zhang H. Fabrication of redox-responsive doxorubicin and paclitaxel prodrug nanoparticles with microfluidics for selective cancer therapy. Biomater Sci. 2019;7(2):634–644.
  14. Fukuizumi A, Minegishi Y, Omori M, et al. Weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer complicated by idiopathic interstitial pneumonias: A single-arm phase II study. Int J Clin Oncol. 2019;24(12):1543–1548.
  15. Zou L, Wang D, Hu Y, et al. Drug resistance reversal in ovarian cancer cells of paclitaxel and borneol combination therapy mediated by PEG-PAMAM nanoparticles. Oncotarget. 2017;8(36):60453–60468.
  16. Hoch MA, Cousins K, Nartey R, Riley K, Hartranft M. Two cases of combination therapy with cetuximab, paclitaxel, and cisplatin for advanced head and neck cancer. J Oncol Pharm Pract. 2018;24(7):553–554.
  17. Xie HJ, Zhao J, Zhuo-Ma D, Zhan-Dui N, Er-Bu A, Tsering T. Inhibiting tumour metastasis by DQA modified paclitaxel plus ligustrazine micelles in treatment of non-small-cell lung cancer. Artif Cells Nanomed Biotechnol. 2019;47(1):3465–3477.
  18. Takashima T, Kawajiri H, Nishimori T, et al. Safety and efficacy of low-dose nanoparticle albumin-bound paclitaxel for HER2-negative metastatic breast cancer. Anticancer Res. 2018;38(1):379–383.
  19. Mendez-Pertuz M, Martinez P, Blanco-Aparicio C, et al. Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun. 2017;8(1):1278.
  20. Qu Y, Hao C, Xu J, et al. ILK promotes cell proliferation in breast cancer cells by activating the PI3K/Akt pathway. Mol Med Rep. 2017;16(4):5036–5042.
  21. Zheng P, Dong L, Zhang B, et al. Long noncoding RNA CASC2 promotes paclitaxel resistance in breast cancer through regulation of miR-18a-5p/CDK19. Histochem Cell Biol. 2019;152(4):281–291.
  22. Hu J, Zhang N, Wang R, Huang F, Li G. Paclitaxel induces apoptosis and reduces proliferation by targeting epidermal growth factor receptor signaling pathway in oral cavity squamous cell carcinoma. Oncol Lett. 2015;10(4):2378–2384.
  23. Liu M, Gong C, Xu R, et al. MicroRNA-5195-3p enhances the chemosensitivity of triple-negative breast cancer to paclitaxel by downregulating EIF4A2. Cell Mol Biol Lett. 2019;24:47.
  24. Kumari S, Mohan MG, Shailender G, et al. Synergistic enhancement of apoptosis by coralyne and paclitaxel in combination on MDA-MB-231, a triple-negative breast cancer cell line. J Cell Biochem. 2019;120(10):18104–18116.
  25. Freitas M, Alves V, Sarmento-Ribeiro AB, Mota-Pinto A. Combined effect of sodium selenite and docetaxel on PC3 metastatic prostate cancer cell line. Biochem Biophys Res Commun. 2011;408(4):713–719.
  26. Xiang XY, Kang JS, Yang XC, et al. SIRT3 participates in glucose metabolism interruption and apoptosis induced by BH3 mimetic Si in ovarian cancer cells. Int J Oncol. 2016;49(2):773–784.
  27. Lv J, Liang Y, Tu Y, Chen J, Xie Y. Hypoxic preconditioning reduces propofol-induced neuroapoptosis via regulation of Bcl-2 and Bax and downregulation of activated caspase-3 in the hippocampus of neonatal rats. Neurol Res. 2018;40(9):767–773.
  28. Peng X, Chen K, Chen J, et al. Aflatoxin B1 affects apoptosis and expression of Bax, Bcl-2, and caspase-3 in thymus and bursa of fabricius in broiler chickens. Environ Toxicol. 2016;31(9):1113–1120.
  29. Ismail IA, Ei-Sokkary GH, Saber SH. Low doses of paclitaxel repress breast cancer invasion through DJ-1/KLF17 signaling pathway. Clin Exp Pharmacol Physiol. 2018;45:961–968.
  30. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666–2676.
  31. Kerenidi T, Kazakou AP, Lada M, et al. Clinical significance of circulating osteopontin levels in patients with lung cancer and correlation with VEGF and MMP-9. Cancer Invest. 2016;34(8):385–392.
  32. Jiang Z, Zhang SJ, Chen B, et al. Paclitaxel inhibited proliferation and matrix metalloproteinases (MMP-2, MMP-9) expression in ovarian cancer HO8910 cells. Chinese Journal of Pharmaceutical Analysis. 2002;22:458–460.
  33. Ren F, Su H, Jiang H, Chen Y. Overexpression of miR-623 suppresses progression of hepatocellular carcinoma via regulating the PI3K/Akt signaling pathway by targeting XRCC5. J Cell Biochem. 2020;121(34):213–223.
  34. Zhu X, Jiang H, Li J, Xu J, Fei Z. Anticancer effects of Paris saponins by apoptosis and PI3K/AKT pathway in gefitinib-resistant non-small cell lung cancer. Med Sci Monit. 2016;22:1435–1441.
  35. Meng Q, Xia C, Fang J, Rojanasakul Y, Jiang B-H. Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway. Cell Sign. 2006;18(12):2262–2271.
  36. Sun C, Tao Y, Gao Y, et al. F-box protein 11 promotes the growth and metastasis of gastric cancer via PI3K/AKT pathway-mediated EMT. Biomed Pharmacother. 2018;98:416–423.
  37. Liu T, Guo J, Zhang X. MiR-202-5p/PTEN mediates doxorubicin-resistance of breast cancer cells via PI3K/Akt signaling pathway. Cancer Biol Ther. 2019;20(7):989–998.
  38. Li N, Miao Y, Shan Y, et al. MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer. Cell Death Dis. 2017;8(5):e2796.