Effect of Scutellarin on Promoting the Sensitivity of Breast Cancer 4T1 Cells to Cisplatin <i>in Vitro</i> and <i>in Vivo</i>

ZHANG Qi; BAO Xiaobo; TIAN Chongchong

doi:10.13386/j.issn1002-0306.2023050219

Volume 45 Issue 5

Feb. 2024

Turn off MathJax

Article Contents

Abstract

References

Supplements

Science and Technology of Food Industry > 2024 > 45(5): 331-340. > DOI: 10.13386/j.issn1002-0306.2023050219

ZHANG Qi, BAO Xiaobo, TIAN Chongchong. Effect of Scutellarin on Promoting the Sensitivity of Breast Cancer 4T1 Cells to Cisplatin in Vitro and in Vivo[J]. Science and Technology of Food Industry, 2024, 45(5): 331−340. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023050219.

Citation:

PDF (9548 KB)

Effect of Scutellarin on Promoting the Sensitivity of Breast Cancer 4T1 Cells to Cisplatin in Vitro and in Vivo

Department of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng 224005, China

More Information

Received Date: May 17, 2023
Available Online: January 01, 2024

Graphical Abstract

Abstract

Abstract

To detect the effect of scutellarin (SCU) on promoting the sensitivity of breast cancer 4T1 cells to cisplatin (CDDP), and the molecular mechanism as well. CCK-8, scratch assay, Transwell assay and flow cytometry were employed to investigate the effects of SCU combined with CDDP on the proliferation, migration, invasion and apoptosis of 4T1 cells in vitro. Then, the 4T1 tumor-bearing mouse model was established to explore the effect of SCU combined with CDDP on tumor growth in vivo. The morphology, necrotic area and microvascular density of tumor tissues were observed by H&E staining. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and proteins expression of apoptosis factors in tumor tissues. The results showed that SCU (200 μmol/L) combined with CDDP (80 μmol/L) significantly inhibited the in vitro proliferation of 4T1 cells (P<0.01). Moreover, the migration and invasion capacity of 4T1 cell were apparently reduced and the apoptosis of tumor cells were significantly promoted when treated with SCU (200 μmol/L) combined with CDDP (80 μmol/L) (P<0.01). Besides, the growth of 4T1 cells in vivo was remarkably slower after administration of 60 mg/kg SCU combined with 3.0 mg/kg CDDP (P<0.01). Further H&E semi-quantitative results revealed the microvascular density of 4T1 tumor tissues was significantly decreased (P<0.01). What’s more, the combination of SCU and CDDP significantly promoted the expression of pro-apoptotic factors Caspase-3, Bax, Caspase-9, Cleaved-Caspase-3 and Cleaved-Caspase-9 (P<0.01) and inhibited the expression of anti-apoptotic factor Bcl-2 in tumor tissues (P<0.05). In conclusion, SCU combined with CDDP could inhibit the function of tumor cells by enhancing the sensitivity of 4T1 cells to CDDP, and also regulate the expression of apoptosis factors, thus inhibiting the growth of tumor.
- scutellarin,
- breast cancer,
- cisplatin,
- sensitivity

FullText(HTML)

References (31)

References

[1]	SHIEN T, IWATA H. Adjuvant and neoadjuvant therapy for breast cancer[J]. Japanese Journal of Clinical Oncology,2020,50(3):225−229. doi: 10.1093/jjco/hyz213
[2]	LEE J S, YOST S E, YUAN Y. Neoadjuvant treatment for triple negative breast cancer:Recent progresses and challenges[J]. Cancers,2020,12(6):1404. doi: 10.3390/cancers12061404
[3]	于红, 张龙梅. 正元胶囊联合新辅助化疗治疗三阴性乳腺癌临床观察[J]. 中国中医药现代远程教育,2023,21(5):129−132. [YU H, ZHANG L M. Clinical observation on Zhengyuan capsule combined with neoadjuvant chemotherapy in the treatment of triple negative breast cancer[J]. Chinese Medicine Modern Distance Education of China,2023,21(5):129−132.] doi: 10.3969/j.issn.1672-2779.2023.05.048 YU H, ZHANG L M. Clinical observation on Zhengyuan capsule combined with neoadjuvant chemotherapy in the treatment of triple negative breast cancer[J]. Chinese Medicine Modern Distance Education of China, 2023, 21（5）: 129−132. doi: 10.3969/j.issn.1672-2779.2023.05.048
[4]	BAI X, NI J, BERETOV J, et al. Triple-negative breast cancer therapeutic resistance:Where is the Achilles' heel?[J]. Cancer Letters,2021,497:100−111. doi: 10.1016/j.canlet.2020.10.016
[5]	ZHANG R, YANG Y, DONG W, et al. D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1[J]. Proceedings of the National Academy of Sciences,2022,119(8):e2114851119. doi: 10.1073/pnas.2114851119
[6]	WON K A, SPRUCK C. Triple-negative breast cancer therapy:Current and future perspectives[J]. International Journal of Oncology,2020,57(6):1245−1261. doi: 10.3892/ijo.2020.5135
[7]	YIN L, DUAN J J, BIAN X W, et al. Triple-negative breast cancer molecular subtyping and treatment progress[J]. Breast Cancer Research,2020,22(1):61. doi: 10.1186/s13058-020-01296-5
[8]	祁冶, 潘海婷, 王秀梅. SCR7对三阴性乳腺癌顺铂化疗的增敏作用研究[J]. 重庆医科大学学报,2023,48(2):220−225. [QI Y, PAN H T, WANG X M. Study on the sensitizing effect of SCR7 on cisplatin chemotherapy in triple-negative breast cancer[J]. Journal of Chongqing Medical University,2023,48(2):220−225.] QI Y, PAN H T, WANG X M. Study on the sensitizing effect of SCR7 on cisplatin chemotherapy in triple-negative breast cancer[J]. Journal of Chongqing Medical University, 2023, 48（2）: 220−225.
[9]	ECKSTEIN N. Platinum resistance in breast and ovarian cancer cell lines[J]. Journal of Experimental & Clinical Cancer Research,2011,30:1−11.
[10]	CARAMELO O, SILVA C, CARAMELO F, et al. The effect of neoadjuvant platinum-based chemotherapy in BRCA mutated triple negative breast cancers-systematic review and meta-analysis[J]. Hereditary Cancer in Clinical Practice,2019,17:1−10.
[11]	TORRISI R, ZURADELLI M, AGOSTINETTO E, et al. Platinum salts in the treatment of BRCA-associated breast cancer:A true targeted chemotherapy[J]. Critical Reviews in Oncology/Hematology,2019,135:66−75. doi: 10.1016/j.critrevonc.2019.01.016
[12]	REDDY S M, BARCENAS C H, SINHA A K, et al. Long-term survival outcomes of triple-receptor negative breast cancer survivors who are disease free at 5 years and relationship with low hormone receptor positivity[J]. British Journal of Cancer,2018,118(1):17−23. doi: 10.1038/bjc.2017.379
[13]	刘涛. 一种游戏茶饮及其制备方法:云南, CN107006648A[P]. 2017-08-04. [LIU T. A kind of tea drink and its preparation method:Yunnan, CN107006648A[P]. 2017-08-04.] LIU T. A kind of tea drink and its preparation method: Yunnan, CN107006648A[P]. 2017-08-04.
[14]	苟秀芹. 一种即食剁椒豆干:山东, CN201510999706.8[P]. 2016-04-13. [GOU X Q. A kind of instant dried tofu with chopped chili:Shandong, CN201510999706.8[P]. 2016-04-13.] GOU X Q. A kind of instant dried tofu with chopped chili: Shandong, CN201510999706.8[P]. 2016-04-13.
[15]	钱卫萍. 一种抑菌牙膏:江苏, CN201711204455.5[P]. 2018-02-09. [QIAN W P. A kind of bacteriostatic toothpaste:Jiangsu, CN201711204455.5[P]. 2018-02-09.] QIAN W P. A kind of bacteriostatic toothpaste: Jiangsu, CN201711204455.5[P]. 2018-02-09.
[16]	DAI J, LI C, ZHAO L, et al. Scutellarin protects the kidney from ischemia/reperfusion injury by targeting Nrf2[J]. Nephrology,2022,27(8):690−700. doi: 10.1111/nep.14069
[17]	PENG L, WEN L, SHI Q F, et al. Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation[J]. Cell Death & Disease,2020,11(11):978.
[18]	ZENG S, CHEN L, SUN Q, et al. Scutellarin ameliorates colitis-associated colorectal cancer by suppressing Wnt/β-catenin signaling cascade[J]. European Journal of Pharmacology,2021,906:174253. doi: 10.1016/j.ejphar.2021.174253
[19]	ZHANG G Y, CHEN W Y, LI X B, et al. Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway[J]. Open Life Sciences,2021,16(1):961−968. doi: 10.1515/biol-2021-0085
[20]	CHEN S, LI R, CHEN Y, et al. Scutellarin enhances anti-tumor immune responses by reducing TNFR2-expressing CD4⁺ Foxp3⁺ regulatory T cells[J]. Biomedicine & Pharmacotherapy,2022,151:113187.
[21]	JU S H, TAN L R, LIU P W, et al. Scutellarin regulates osteoarthritis in vitro by inhibiting the PI3K/AKT/mTOR signaling pathway[J]. Molecular Medicine Reports,2021,23(1):1.
[22]	田冲冲, 张琦, 包小波, 等. 灯盏花乙素对黑色素瘤B16体内外的作用及机制研究[J]. 食品工业科技,2023,44(17):406−412. [TIAN C C, ZHANG Q, BAO X B, et al. Effect of scutellarin on melanoma B16 in vitro and in vivo and its mechanism[J]. Science and Technology of Food Industry,2023,44(17):406−412.] TIAN C C, ZHANG Q, BAO X B, et al. Effect of scutellarin on melanoma B16 in vitro and in vivo and its mechanism[J]. Science and Technology of Food Industry, 2023, 44（17）: 406−412.
[23]	姚侠, 方杭, 金鑫. 灯盏乙素通过下调TRIM32的表达增强卡铂的抗卵巢癌活性研究[J]. 中国现代应用药学,2020,37(3):282−287. [YAO X, FANG H, JIN X. Scutellarin enhances carboplatin-induced cytotoxicity against ovarian cancer by decrease the expression of TRIM32[J]. Chinese Journal of Modern Applied Pharmacy,2020,37(3):282−287.] YAO X, FANG H, JIN X. Scutellarin enhances carboplatin-induced cytotoxicity against ovarian cancer by decrease the expression of TRIM32[J]. Chinese Journal of Modern Applied Pharmacy, 2020, 37（3）: 282−287.
[24]	GAO C, ZHOU Y, JIANG Z, et al. Cytotoxic and chemosensitization effects of scutellarin from traditional Chinese herb Scutellaria altissima L. in human prostate cancer cells[J]. Oncology Reports,2017,8(3):1491−1499.
[25]	CAO Y, FENG Y H, GAO L W, et al. Artemisinin enhances the anti-tumor immune response in 4T1 breast cancer cells in vitro and in vivo[J]. International Immunopharmacology,2019,70:110−116. doi: 10.1016/j.intimp.2019.01.041
[26]	张媛, 禹卓玥, 孙立新, 等. 卵巢癌组织MEOX1表达对细胞增殖和侵袭及迁移影响[J]. 中华肿瘤防治杂志,2020,27(4):262−268. [ZHANG Y, YU Z Y, SUN L X, et al. Expression of MEOX1 in ovarian cancer and its effect on the proliferation, invasion and migration[J]. Chinese Journal of Cancer Prevention and Treatment,2020,27(4):262−268.] ZHANG Y, YU Z Y, SUN L X, et al. Expression of MEOX1 in ovarian cancer and its effect on the proliferation, invasion and migration[J]. Chinese Journal of Cancer Prevention and Treatment, 2020, 27（4）: 262−268.
[27]	PULASKI B A, OSTRAND-ROSENBERG S. Mouse 4T1 breast tumor model[J]. Current Protocols in Immunology, 2000, 39(1):20.2. 1-20.2. 16.
[28]	CHANGIZI Z, MOSLEHI A, ROHANI A H, et al. Chlorogenic acid induces 4T1 breast cancer tumor's apoptosis via p53, Bax, Bcl-2, and caspase-3 signaling pathways in BALB/c mice[J]. Journal of Biochemical and Molecular Toxicology,2021,35(2):e22642. doi: 10.1002/jbt.22642
[29]	DA SILVA LAWISCH G K, BIOLCHI V, et al. The role of FASL, BCL-2 and BAX polymorphisms in Brazilian patients with prostate cancer and benign prostatic hyperplasia[J]. Molecular Biology Reports,2022,49(10):9445−9451. doi: 10.1007/s11033-022-07805-3
[30]	WANG H W, ZHAO W P, LIU J, et al. Fluoride-induced oxidative stress and apoptosis are involved in the reducing of oocytes development potential in mice[J]. Chemosphere,2017,186:911−918. doi: 10.1016/j.chemosphere.2017.08.068
[31]	WANG S, ZHANG Y, GAO J, et al. The enantioselective study of the toxicity effects of chiral acetochlor in HepG2 cells[J]. Ecotoxicology and Environmental Safety,2021,218:112261. doi: 10.1016/j.ecoenv.2021.112261

[1]	CHEN Jiangkui, LI Jing, YIN Chunyan, LIAN Qimeng, YE Jia. Effects of Four Kinds of Antioxidants on the Oxidative Stability of Xanthoceras sorbifolia Bunge Oil and Analysis of Its Fatty Acid Compositions[J]. Science and Technology of Food Industry, 2022, 43(12): 70-76. DOI: 10.13386/j.issn1002-0306.2021090033
[2]	LI Yuan-yuan, PAN Ling, ZHANG Yan. Effects of natural antioxidants on the oxidative stability and flavor characteristics of peanut oil[J]. Science and Technology of Food Industry, 2018, 39(5): 241-249.
[3]	WU Chen, CHEN Yi, MEI Jiang, ZHANG Zhi-hong, WANG Yu-ting. Studies of oxidative stability and the mechanisms of antioxidants in emulsions[J]. Science and Technology of Food Industry, 2015, (24): 380-384. DOI: 10.13386/j.issn1002-0306.2015.24.075
[4]	LEI Jing-ling, ZHAO Zhong-xing, WANG Chao-yang, ZHU Chang-jie, FENG Li-jin, LU Qiang-ji. Study on thermal stability and thermal inactivation kinetics of immobilized earthworm fibrinolytic enzyme[J]. Science and Technology of Food Industry, 2015, (21): 107-110. DOI: 10.13386/j.issn1002-0306.2015.21.013
[5]	MIAO Sen, WANG Lu, WANG Xiao-biao, QI Tian, ZHAO Zhi-wei, WU Yun. Research of the influence factors of thermal stability of Fresh Mare's Milk[J]. Science and Technology of Food Industry, 2015, (15): 213-218. DOI: 10.13386/j.issn1002-0306.2015.15.036
[6]	WANG Meng, DU Bing, CAO Wei. Research of activity and thermal stability of GOD in jujube and buckwheat honeys[J]. Science and Technology of Food Industry, 2015, (09): 83-86. DOI: 10.13386/j.issn1002-0306.2015.09.009
[7]	LIU Li-li, LI Si-dong, TANG Bing, YANG Xi-hong, LI Pu-wang, YANG Zi-ming. Study on the thermal stability of chitosan/gelatin composite films for food preservation[J]. Science and Technology of Food Industry, 2014, (08): 310-312. DOI: 10.13386/j.issn1002-0306.2014.08.062
[8]	Enzymatic characteristics and thermal stability model of polyphenol oxidase from potato[J]. Science and Technology of Food Industry, 2012, (19): 92-96. DOI: 10.13386/j.issn1002-0306.2012.19.035
[9]	Study on screening of efficient multiple antioxidants and stability of algal oil[J]. Science and Technology of Food Industry, 2012, (18): 318-321. DOI: 10.13386/j.issn1002-0306.2012.18.046
[10]	一品红红色素的提取及其稳定性研究[J]. Science and Technology of Food Industry, 1999, (06): 24-26. DOI: 10.13386/j.issn1002-0306.1999.06.068

Supplements (1)

Supplements
Other Related Supplements

Cited By

Cited by

Periodical cited type(11)

1.	杨集镪，曾穗雯. 原子荧光光谱仪测定食品中汞含量的研究. 食品安全导刊. 2023(01): 111-113 .
2.	程梦蓉，蒋国振，王婧，吴静，姬玲霞. 直接测汞仪测定大米粉中总汞含量的不确定度评定. 粮食与食品工业. 2023(03): 53-58 .
3.	梁良，杜雨馨，杨子建. 基于支持向量机的多环芳烃光谱定量分析. 激光杂志. 2023(06): 220-224 .
4.	金凯. 测汞仪直接测定水中汞的不确定度评定. 现代食品. 2023(23): 166-169 .
5.	赵忠良. 原子荧光仪在地质矿物硒元素测定中的应用. 化工管理. 2022(18): 103-105 .
6.	姚成虎，王滢，杨启鹏，洪成山，王岁岁，孙涓，毛小庆. 电感耦合等离子质谱法测定蟹黄中4种重金属含量的不确定度评定. 现代农业科技. 2022(18): 155-159+164 .
7.	张阔，冯金奎，鄂立军. 照度测量不确定度研究. 中国特种设备安全. 2022(10): 22-25+41 .
8.	王娟，华蓉，游金坤，邓雅元，孙达锋，杨璐敏，吴素蕊. 影响食用菌总汞含量测定准确度的关键技术探索. 中国食用菌. 2022(11): 60-66 .
9.	贺璐，郑静. 电感耦合等离子体发射光谱法测定食品中钙、镁、磷、铁、锌、锰含量的不确定度评定. 化学分析计量. 2022(12): 83-87 .
10.	李娟，辜芸，谭洪涛，周鸿. 婴幼儿食品中总汞含量检测方法的研究. 实验与检验医学. 2022(05): 524-525+546 .
11.	程君，卢嘉砾，余松柏. 催化热解-冷原子吸收分光光度法测定石膏中总汞的不确定度评定. 中国水泥. 2022(S1): 16-21 .