附子提取物对肺癌A549细胞增殖抑制及放射增敏作用的研究

doi:10.3969/j.issn.1004-616x.2022.03.010

Abstract

Abstract: OBJECTIVE: To study effects of Fuzi (aconite) extracts on proliferation and radiosensitization of human lung cancer A549 cells. METHODS: The cells were cultured and were divided into 4 groups:control,Fuzi extract,X-ray-irradiated,and Fuzi plus X-ray-irradiated groups. The control group was given culture medium,the Fuzi extract group was treated with IC₂₀ 30 μg/mL of Fuzi extract,the radiation group was given X-ray-irradiated,and the Fuzi plus X-ray-irradiated group were first treated with the Fuzi extract and then X-ray. After treatments,cell proliferation was detected by CCK-8 assay and colony formation assay was used to measure cell survival. Single-hit multi-target model was used to fit the survival curve and to calculate the sensitive enhancement ratio (SER). Apoptosis rates were detected by flow cytometry,and protein expression levels of Bax and Bcl-2 were detected by Western blot. RESULTS: Fuzi extract concentrations(<20 μg/mL) enhanced viability of A549 cells but increasing concentrations (>30 μg/mL) inhibited growth of the cells in a dose-dependent manner. The shoulder at the beginning of the survival curve in the Fuzi plus X-ray-irradiated group was slightly narrower, and the D₀values in the X-ray-irradiated and Fuzi plus X-ray-irradiated group were 1.83 Gy,1.48 Gy,and the SER was 1.24,respectively. The apoptosis rates were significantly increased in the Fuzi plus X-ray-irradiated group and were higher than that in both the Fuzi and X-ray irradiation groups (P<0.05). The results of Western blot show that protein expressions of Bax were increased but were decreased for Bcl-2 in the Fuzi extract versus the X-ray-irradiated groups. Bax and Bcl-2 protein levels were changed more significantly in the Fuzi plus X-ray-irradiated than the other groups (P<0.01). CONCLUSION: Fuzi extract at 30 μg/mL inhibited proliferation and enhanced radiosensitizing effects on human lung cancer A549 cells,and the mechanism may be related to the induction of apoptosis.

Key words: lung neoplasms, Fuzi extraction, Chinese medicine treatment, radiotherapy, radiosentization, cell apoptosis

CLC Number:

R730.1

ZHANG Qi, LIU Yujun, ZHUANG Xibing, QIAO Tiankui. Fuzi extracts on proliferation and radiosensitization of lung cancer A549 cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(3): 227-232.

References

[1] CHEN W Q, ZHENG R S, BAADE P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[2] SHER D J, KOSHY M, LIPTAY M J, et al. Influence of conformal radiotherapy technique on survival after chemoradiotherapy for patients with stage III non-small cell lung cancer in the National Cancer Data Base[J]. Cancer, 2014,120(13):2060-2068.
[3] MEDFORD-DAVIS L, DECAMP M, RECHT A, et al. Surgical management of early-stage non-small cell lung carcinoma and the present and future roles of adjuvant therapy:a review for the radiation oncologist[J]. Int J Radiat Oncol Biol Phys, 2012,84(5):1048-1057.
[4] PORTUGAL J, MANSILLA S, BATALLER M. Mechanisms of drug-induced mitotic catastrophe in cancer cells[J]. Curr Pharm Des, 2010, 16(1):69-78.
[5] KIM B M, HONG Y, LEE S, et al. Therapeutic implications for overcoming radiation resistance in cancer therapy[J]. Int J Mol Sci, 2015, 16(11):26880-26913.
[6] KELLY P N, STRASSER A. The role of Bcl-2 and its prosurvival relatives in tumourigenesis and cancer therapy[J]. Cell Death Differ, 2011, 18(9):1414-1424.
[7] JENDROSSEK V. The intrinsic apoptosis pathways as a target in anticancer therapy[J]. Curr Pharm Biotechnol, 2012, 13(8):1426-1438.
[8] LI H S, SUN M N, XU J, et al. Immunological response in H22transplanted mice undergoing Aconitum coreanum polysaccharide treatment[J]. Int J Biol Macromol, 2013, 55:295-300.
[9] GAO T T, BI H T, MA S, et al. The antitumor and immunostimulating activities of water soluble polysaccharides from Radix Aconiti, Radix Aconiti Lateralis and Radix Aconiti Kusnezoffii[J]. Nat Prod Commun, 2010, 5(3):447-455.
[10] ZHAO Y L, BU Q, ZHOU Y, et al. Mechanism study of Aconitum-induced neurotoxicity in PC12 cells:involvement of dopamine release and oxidative damage[J]. Neurotoxicology,2010, 31(6):752-757.
[11] CHEN D, CAO R, HE J H, et al. Synergetic effects of aqueous extracts of Fuzi(Radix Aconiti Lateralis Preparata)and Tubeimu(Rhizoma Bolbostemmatis)on MDA-MB-231 and SKBR3 cells[J]. J Tradit Chin Med, 2016, 36(1):113-124.
[12] 刘蕾,张琼玲,王继永,等.制附子水提物的生物活性限值测定研究[J].中国药物警戒, 2020, 17(2):75-80.
[13] SHORT S C, GIAMPIERI S, WORKU M, et al. Rad51inhibition is an effective means of targeting DNA repair in glioma models and CD133+tumor-derived cells[J]. Neurooncology, 2011, 13(5):487-499.
[14] XING N, QIAO T K, ZHUANG X B, et al. CpG oligodeoxyribonucleotide 7909 enhances radiosensitivity via downregulating Oct-4 expression in radioresistant lung cancer cells[J]. Onco Targets Ther, 2015, 8:1443-1449.
[15] 朱潇雨,吴喆,高瑞柯,等.从“阳虚毒结”角度探讨化疗耐药形成及温阳法干预机理[J].中医杂志, 2021, 62(8):672-676.
[16] 张向农,王欣,王梅,等. 355例肿瘤患者中医体质类型流行病学调查研究[J].中国中医药信息杂志, 2010, 17(5):13-16.
[17] 陈荣昌,孙桂波,张强,等.附子及其复方中药的药理作用研究进展[J].中草药, 2014, 45(6):883-888.
[18] 曹志友,金宏,田晶,等.白附子提取物对胶质瘤细胞的增殖抑制和诱导凋亡作用及其机制[J].吉林大学学报:医学版,2013, 39(4):649-652, 863.
[19] 丁芸霞,邹玺,吴坚,等.附子生物碱对人胃癌细胞株SGC-7901凋亡及细胞周期的影响[J].世界科学技术-中医药现代化, 2013, 15(5):915-919.
[20] QI X Z, WANG L, WANG H, et al. Aconitine inhibits the proliferation of hepatocellular carcinoma by inducing apoptosis[J]. Int J Clin Exp Pathol, 2018, 11(11):5278-5289.
[21] SUN L B, WANG Z J, WANG H L, et al. Polysaccharide sulphated derivative from Aconitum coreanum induces cell apoptosis in the human brain glioblastoma U87MG cell line via the NF-κB/Bcl-2 cell apoptotic signaling pathway[J]. Oncol Rep, 2018, 39(3):1469-1474.
[22] KALE J, LIU Q, LEBER B, et al. Shedding light on apoptosis at subcellular membranes[J]. Cell, 2012, 151(6):1179-1184.
[23] HARADA A, MATSUZAKI K, TAKEIRI A, et al. The predominant role of apoptosis in γH2AX formation induced by aneugens is useful for distinguishing aneugens from clastogens[J]. Mutat Res Toxicol Environ Mutagen, 2014, 771:23-29.
[24] WENSVEEN F M, ALVES N L, DERKS I A M, et al. Apoptosis induced by overall metabolic stress converges on the Bcl-2family proteins Noxa and Mcl-1[J]. Apoptosis, 2011, 16(7):708-721.

Fuzi extracts on proliferation and radiosensitization of lung cancer A549 cells

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	JIAO Wenjing, GUO Xiujuan, MA Ming, SHAO Junguo, ZHANG Jinyan. Comparative efficacies between concurrent chemo-radiotherapy and radiotherapy alone in elderly patients with locally advanced esophageal cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(2): 124-128.
[2]	LI Peng, MA Kun, WU Haoyu, WU Yanping, LI Baixiang. Mechanism of isoflavones protection of SH-SY5Y cells from atrazine [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(1): 25-30.
[3]	AYIGULI·Hare, LU Yanrong, YISIKANDA·Abulimiti, ZHANG Jinrong. Expression of the LGR5 gene in rectal cancer in response to neoadjuvant chemoradiotherapy [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(1): 60-64,69.
[4]	ZHOU Qiming, LI Wei, YUAN Jianhui, ZHAO Yan, DUAN Jiangman, XIONG Donglin. Abnormal expression of TGF-β1 in melanoma patients and its inhibitory effect on tumor cell proliferation [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(5): 348-352.
[5]	FU Ying, ZHAO Chen, CHANG Zhenzhan, LIN Huaying, SUN Zhenxiao. Inhibition effects of Arca subcrenata Lischke anticancer protein on human breast carcinoma MCF-7 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2015, 27(6): 415-420.
[6]	GAO Caixia, QIAO Tiankui, ZHANG Bin, YUAN Sujuan. Effect of Toll-like receptor 9 expression in postoperative radiotherapy in lung cancer survivors [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2015, 27(4): 294-298.
[7]	QIN Xu-jun，HE Wei，HAI Chun-xu*. Role of protein Bcl-2 in the oxidative injury induced by radiotherapy or chemotherapy [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2014, 26(5): 361-364.
[8]	SONG Wei，YANG Hai-bo，CHEN Lan-ying*. Effects of curcumin on related gene expression during HaCaT cell apoptosis [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2014, 26(4): 254-257.
[9]	XIONG Meng-zhen，ZHANG Juan，SUN Rong-li，YIN Li-hong，PU Yue-pu. Apoptotic effect and regulatory mechanism of 1, 4-benzoquinone on HELF cells [J]. , 2012, 24(1): 6-9.
[10]	RUI Meng，CONG Mei，DUAN Yun-you，HOU Chun-mei. Study of paclitaxel effects on human lung cancer cell lines with different p53 genotype [J]. , 2012, 24(1): 14-19.
[11]	WU Li-rui，LI Hong-xia，WANG Lan-peng，WANG De-hua，SUN Sha. Evaluation of DNA damage induced by radiotherapy in cervical cancer patients [J]. , 2011, 23(4): 291-293.
[12]	LI Qi-feng, WU Ming-yao. The expression of EGFR, VEGFR1/Flt_1 in esophageal squamous cell carcinoma tissues with or without radiotherapy [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2010, 22(5): 386-390.
[13]	WANG Lu, REN Xing, AO Lin, PANG Xue-li, ZHANG Li-shi, CAO Jia, . DNA Damage in Nasopharyngeal Cancer Patients Undergoing Radiotherapy [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2009, 21(4): 268-270.
[14]	RUI Meng, LIU Chang-ting, DUAN Yun-you, YU Xiao-dan, HOU Chun-mei.. (2. Growth-inhibiting Effects of Paclitaxel on p53-deficientStrain of Human Lung Cancer H1299 Cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2008, 20(3): 193-197.
[15]	ZHAO Wen-hong, ZHUANG Ying, ZHAO Hong, ZHANG Ding. Human Umbilical Vein Endothelial Cell Apoptosis and Its Proliferative Inhibition Induced by Cholesterin [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2007, 19(6): 453-456.