A preliminary mechanistic exploration of the effect of leptin on the docetaxel sensitivity of MDA‑MB‑231 triple‑negative breast cancer cells

Gao,Simeng; Ding,Sijuan; Tang,Zhaohui

doi:10.3892/mco.2024.2722

A preliminary mechanistic exploration of the effect of leptin on the docetaxel sensitivity of MDA‑MB‑231 triple‑negative breast cancer cells

Authors:
- Simeng Gao
- Sijuan Ding
- Zhaohui Tang
View Affiliations

Affiliations: Department of Oncology, The Central Hospital of Yongzhou, Yongzhou, Hunan 425000, P.R. China
Published online on: February 1, 2024 https://doi.org/10.3892/mco.2024.2722
Article Number: 24
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Breast cancer is a common tumor encountered in women, and triple‑negative breast cancer (TNBC) has an extremely poor prognosis. The effect of leptin on the docetaxel sensitivity of MDA‑MB‑231 TNBC cells has not been investigated. The present study aimed to clarify the effect of leptin and M2 tumor‑associated macrophages (TAMs) on the chemosensitivity of TNBC cell lines and its possible mechanisms. In the present study, the apoptosis of the MDA‑MB‑231 cell line was detected at 0, 24, 48 and 72 h using a Cell Counting Kit‑8 assay to determine the appropriate concentration of docetaxel as well as the IC₅₀ value. After determining the effect of leptin on TAMs, the conditioned medium with an appropriate concentration of docetaxel was collected to treat the breast cancer cells, and flow cytometry was used to detect the cell cycle distribution and apoptosis in different treatment groups. Interleukin 8 (IL‑8) expression was detected using ELISA and western blot assay. The IL‑8 antibody was used to neutralize IL‑8, and invasion and scratch assays were used to detect changes in invasion and migration of breast cancer cells. Statistical analysis was performed using GraphPad Prism 9.0 and SPSS 22.0. It was revealed that the apoptotic rate of MDA‑MB‑231 cells in the leptin‑treated TAMs group was lower than that in other groups. The expression of IL‑8 was notably elevated in the group treated with leptin‑activated TAMs compared with that in the other groups. The neutralization of IL‑8 resulted in a significant reduction in the invasive migration of MDA‑MB‑231 cells compared with that in the non‑neutralized group.

View Figures

View References

1	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI View Article : Google Scholar
2	Garrido-Castro AC, Lin NU and Polyak K: Insights into molecular classifications of triple-negative breast cancer: Improving patient selection for treatment. Cancer Discov. 9:176–198. 2019.PubMed/NCBI View Article : Google Scholar
3	Li Y, Zhang H, Merkher Y, Chen L, Liu N, Leonov S and Chen Y: Recent advances in therapeutic strategies for triple-negative breast cancer. J Hematol Oncol. 15(121)2022.PubMed/NCBI View Article : Google Scholar
4	Maroni P: Leptin, Adiponectin, and Sam68 in bone metastasis from breast cancer. Int J Mol Sci. 21(1051)2020.PubMed/NCBI View Article : Google Scholar
5	Gu L, Wang CD, Cao C, Cai LR, Li DH and Zheng YZ: Association of serum leptin with breast cancer: A meta-analysis. Medicine (Baltimore). 98(e14094)2019.PubMed/NCBI View Article : Google Scholar
6	Niu J, Jiang L, Guo W, Shao L, Liu Y and Wang L: The association between leptin level and breast cancer: A meta-analysis. PLoS One. 8(e67349)2013.PubMed/NCBI View Article : Google Scholar
7	Pan H, Deng LL, Cui JQ, Shi L, Yang YC, Luo JH, Qin D and Wang L: Association between serum leptin levels and breast cancer risk: An updated systematic review and meta-analysis. Medicine (Baltimore). 97(e11345)2018.PubMed/NCBI View Article : Google Scholar
8	Miyoshi Y, Funahashi T, Tanaka S, Taguchi T, Tamaki Y, Shimomura I and Noguchi S: High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels. Int J Cancer. 118:1414–1419. 2006.PubMed/NCBI View Article : Google Scholar
9	Wang WJ, Lai HY, Zhang F, Shen WJ, Chu PY, Liang HY, Liu YB and Wang JM: MCL1 participates in leptin-promoted mitochondrial fusion and contributes to drug resistance in gallbladder cancer. JCI Insight. 6(e135438)2021.PubMed/NCBI View Article : Google Scholar
10	Chen X, Zha X, Chen W, Zhu T, Qiu J, Røe OD, Li J, Wang Z and Yin Y: Leptin attenuates the anti-estrogen effect of tamoxifen in breast cancer. Biomed Pharmacother. 67:22–30. 2013.PubMed/NCBI View Article : Google Scholar
11	Ma L, Fan Z, Du G and Wang H: Leptin-elicited miRNA-342-3p potentiates gemcitabine resistance in pancreatic ductal adenocarcinoma. Biochem Biophys Res Commun. 509:845–853. 2019.PubMed/NCBI View Article : Google Scholar
12	Li K, Wei L, Huang Y, Wu Y, Su M, Pang X, Wang N, Ji F, Zhong C and Chen T: Leptin promotes breast cancer cell migration and invasion via IL-18 expression and secretion. Int J Oncol. 48:2479–2487. 2016.PubMed/NCBI View Article : Google Scholar
13	Ojalvo LS, King W, Cox D and Pollard JW: High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am J Pathol. 174:1048–1064. 2009.PubMed/NCBI View Article : Google Scholar
14	Nadella V, Garg M, Kapoor S, Barwal TS, Jain A and Prakash H: Emerging neo adjuvants for harnessing therapeutic potential of M1 tumor associated macrophages (TAM) against solid tumors: Enusage of plasticity. Ann Transl Med. 8(1029)2020.PubMed/NCBI View Article : Google Scholar
15	Qian BZ and Pollard JW: Macrophage diversity enhances tumor progression and metastasis. Cell. 141:39–51. 2010.PubMed/NCBI View Article : Google Scholar
16	Li C, Xu X, Wei S, Jiang P, Xue L, Wang J and Senior Correspondence: Tumor-associated macrophages: Potential therapeutic strategies and future prospects in cancer. J Immunother Cancer. 9(e001341)2021.PubMed/NCBI View Article : Google Scholar
17	Cao H, Huang Y, Wang L, Wang H, Pang X, Li K, Dang W, Tang H, Wei L, Su M, et al: Leptin promotes migration and invasion of breast cancer cells by stimulating IL-8 production in M2 macrophages. Oncotarget. 7:65441–65453. 2016.PubMed/NCBI View Article : Google Scholar
18	Fousek K, Horn LA and Palena C: Interleukin-8: A chemokine at the intersection of cancer plasticity, angiogenesis, and immune suppression. Pharmacol Ther. 219(107692)2021.PubMed/NCBI View Article : Google Scholar
19	Cao W, Chen HD, Yu YW, Li N and Chen WQ: Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 134:783–791. 2021.PubMed/NCBI View Article : Google Scholar
20	Seferbekova Z, Lomakin A, Yates LR and Gerstung M: Spatial biology of cancer evolution. Nat Rev Genet. 24:295–313. 2023.PubMed/NCBI View Article : Google Scholar
21	Bejarano L, Jordāo MJC and Joyce JA: Therapeutic targeting of the tumor microenvironment. Cancer Discov. 11:933–959. 2021.PubMed/NCBI View Article : Google Scholar
22	Smrekar K, Belyakov A and Jin K: Crosstalk between triple negative breast cancer and microenvironment. Oncotarget. 14:284–293. 2023.PubMed/NCBI View Article : Google Scholar
23	Singh A, Mayengbam SS, Yaduvanshi H, Wani MR and Bhat MK: Obesity programs macrophages to support cancer progression. Cancer Res. 82:4303–4312. 2022.PubMed/NCBI View Article : Google Scholar
24	Habanjar O, Bingula R, Decombat C, Diab-Assaf M, Caldefie-Chezet F and Delort L: Crosstalk of inflammatory cytokines within the breast tumor microenvironment. Int J Mol Sci. 24(4002)2023.PubMed/NCBI View Article : Google Scholar
25	Saxena NK, Vertino PM, Anania FA and Sharma D: Leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3. J Biol Chem. 282:13316–13325. 2007.PubMed/NCBI View Article : Google Scholar
26	Yuan HJ, Sun KW and Yu K: Leptin promotes the proliferation and migration of human breast cancer through the extracellular-signal regulated kinase pathway. Mol Med Rep. 9:350–354. 2014.PubMed/NCBI View Article : Google Scholar
27	Wang L, Tang C, Cao H, Li K, Pang X, Zhong L, Dang W, Tang H, Huang Y, Wei L, et al: Activation of IL-8 via PI3K/Akt-dependent pathway is involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells. Cancer Biol Ther. 16:1220–1230. 2015.PubMed/NCBI View Article : Google Scholar
28	Grossmann ME, Ray A, Nkhata KJ, Malakhov DA, Rogozina OP, Dogan S and Cleary MP: Obesity and breast cancer: Status of leptin and adiponectin in pathological processes. Cancer Metastasis Rev. 29:641–653. 2010.PubMed/NCBI View Article : Google Scholar
29	Orecchioni S, Reggiani F, Talarico G and Bertolini F: Mechanisms of obesity in the development of breast cancer. Discov Med. 20:121–128. 2015.PubMed/NCBI
30	Riolfi M, Ferla R, Del Valle L, Piña-Oviedo S, Scolaro L, Micciolo R, Guidi M, Terrasi M, Cetto GL and Surmacz E: Leptin and its receptor are overexpressed in brain tumors and correlate with the degree of malignancy. Brain Pathol. 20:481–489. 2010.PubMed/NCBI View Article : Google Scholar
31	Gonzalez-Perez RR, Lanier V and Newman G: Leptin's pro-angiogenic signature in breast cancer. Cancers (Basel). 5:1140–1162. 2013.PubMed/NCBI View Article : Google Scholar
32	Andò S and Catalano S: The multifactorial role of leptin in driving the breast cancer microenvironment. Nat Rev Endocrinol. 8:263–275. 2011.PubMed/NCBI View Article : Google Scholar