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巨噬细胞增强宫颈癌细胞对SN-38的抗性

赖丽梨 靳焕 段华英 邹争志

赖丽梨, 靳焕, 段华英, 邹争志. 巨噬细胞增强宫颈癌细胞对SN-38的抗性[J]. 华南师范大学学报(自然科学版), 2021, 53(1): 63-69. doi: 10.6054/j.jscnun.2021010
引用本文: 赖丽梨, 靳焕, 段华英, 邹争志. 巨噬细胞增强宫颈癌细胞对SN-38的抗性[J]. 华南师范大学学报(自然科学版), 2021, 53(1): 63-69. doi: 10.6054/j.jscnun.2021010
LAI Lili, JIN Huan, DUAN Huaying, ZOU Zhengzhi. Macrophage's Promotion of Cervical Cancer Cell Resistance to SN-38[J]. Journal of South China normal University (Natural Science Edition), 2021, 53(1): 63-69. doi: 10.6054/j.jscnun.2021010
Citation: LAI Lili, JIN Huan, DUAN Huaying, ZOU Zhengzhi. Macrophage's Promotion of Cervical Cancer Cell Resistance to SN-38[J]. Journal of South China normal University (Natural Science Edition), 2021, 53(1): 63-69. doi: 10.6054/j.jscnun.2021010

巨噬细胞增强宫颈癌细胞对SN-38的抗性

doi: 10.6054/j.jscnun.2021010
基金项目: 

国家自然科学基金项目 81772803

国家自然科学基金项目 81972479

广东省自然科学基金项目 2019A1515011100

广州市科技计划项目 201904010038

详细信息
    通讯作者:

    邹争志,Email:zouzhengzhi@163.com

  • 中图分类号: R453.9; R34

Macrophage's Promotion of Cervical Cancer Cell Resistance to SN-38

  • 摘要: 通过GDSC在线软件,分析了SN-38在数据库中8种宫颈癌细胞系对310多种化疗药的半抑制质量浓度(IC50)Z分数值,并选取HPV-18阳性HeLa细胞、HPV-16阳性SiHa和CaSki细胞以及HPV阴性C-33A细胞,经过SN-38处理24、48 h,通过CCK8试验检测了细胞活力来探究巨噬细胞是否介导宫颈癌细胞对SN-38抵抗. THP1被HeLa和SiHa细胞诱导成肿瘤相关巨噬细胞,通过CCK8试验探讨巨噬细胞在宫颈癌细胞对SN-38敏感性中的作用. 结果显示:CaSki、ME-180、HT-3、C-33A对SN-38极敏感,HeLa和SiHa对SN-38敏感,而CAL-39对SN-38不敏感;CaSki和C-33A的IC50值相对于HeLa和SiHa更低,表明CaSki和C-33A对SN-38更敏感;巨噬细胞显著抑制SN-38对HeLa和SiHa细胞的杀伤. 这些结果表明了肿瘤相关巨噬细胞促进宫颈癌细胞对SN-38抵抗.
  • 图  1  宫颈癌细胞系对化疗药的敏感性

    注:蓝色箭头所指的是SN-38代表的数值点,每个点的横坐标代表300多种不同种类药物(具体药物名称见GDSC数据库),每个点的纵坐标指示的是将各药物的半抑制质量浓度(IC50)值进行Z分数(Z-score)数据标准化后的值.

    Figure  1.  The sensitivity of cervical cancer cell to chemotherapy drugs

    图  2  宫颈癌细胞系对SN-38的敏感性

    Figure  2.  The sensitivity of cervical cancer cell to SN-38

    图  3  HeLa、CaSki、C-33A和SiHa细胞加入SN-38 24、48 h后的细胞活力

    注: 数据表示为平均值±标准差,*P < 0.05,* *P < 0.01,下图同.

    Figure  3.  The cell viability of HeLa, CaSki, C-33A and SiHa treated with SN-38 for 24 h and 48 h

    图  4  在HeLa、CaSki、C-33A和SiHa细胞加入SN-38 24、48 h的IC50

    Figure  4.  The IC50 of HeLa, CaSki, C-33A and SiHa were treated with SN-38 for 24 h and 48 h

    图  5  宫颈癌细胞与巨噬细胞共培养48 h后巨噬细胞中HLA-DRCD80CD206CD163ARG1的mRNA水平

    Figure  5.  The levels of HLA-DR, CD80, CD206, CD163 and ARG1 in macrophages cocultured with cervical cancer cells for 48 h

    图  6  宫颈癌细胞经巨噬细胞条件培养液(CM)处理,同时加入SN-38处理24、48 h后的细胞活力

    Figure  6.  The viability of cervical cancer cells when treated with condition media of macrophages and SN-38 for 24 and 48 h

    表  1  引物的名称和序列

    Table  1.   The names and sequences of the primers

    基因名 引物方向 引物序列(5’-3’)
    HLA-DR Forward AGTCCCTGTGCTAGGATTTTTCA
    HLA-DR Reverse ACATAAACTCGCCTGATTGGTC
    CD80 Forward AAACTCGCATCTACTGGCAAA
    CD80 Reverse GGTTCTTGTACTCGGGCCATA
    CD206 Forward AAGGCGGTGACCTCACAAG
    CD206 Reverse AAAGTCCAATTCCTCGATGGTG
    ARG1 Forward CGCCAAGTCCAGAACCATAGG
    ARG1 Reverse TCTCAATACTGTAGGGCCTTCTT
    CD163 Forward ACATAGATCATGCATCTGTCATTTG
    CD163 Reverse CATTCTCCTTGGAATCTCACTTCTA
    β-Actin Forward CATGTACGTTGCTATCCAGGC
    β-Actin Reverse CTCCTTAATGTCACGCACGAT
    下载: 导出CSV
  • [1] ARBYN M, WEIDERPASS E, BRUNI L, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis[J]. The Lancet Global Health, 2019, 8(2): 191-203. http://www.sciencedirect.com/science/article/pii/S2214109X19304826
    [2] COHEN P, JHINGRAN A, OAKNIN A, et al. Cervical cancer[J]. The Lance, 2019, 393(10167): 169-182. doi: 10.1016/S0140-6736(18)32470-X
    [3] SARFATI D, DYER R, SAM L, et al. Cancer control in the Pacific: big challenges facing small island states[J]. The Lancet Oncology, 2019, 20(9): 475-492. doi: 10.1016/S1470-2045(19)30400-0
    [4] KAWATO Y, AONUMA M, HIROTA Y, et al. Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11[J]. Cancer Research, 1991, 51(16): 4187-4191. http://chromsci.oxfordjournals.org/cgi/ijlink?linkType=ABST&journalCode=canres&resid=51/16/4187
    [5] SUN X F, FERREUD L, SVANVIK J, et al. Anticancer effect of SN-38 on colon cancer cell lines with different metastatic potential[J]. Oncology Reports, 2008, 19(6): 1493-1498. http://europepmc.org/abstract/med/18497955
    [6] FRANK A, AGAMA K, ROY A, et al. Characterization of DNA topoisomerase I in three SN-38 resistant human colon cancer cell lines reveals a new pair of resistance-associated mutations[J]. Journal of Experimental & Clinical Cancer Research, 2016, 35(1): 56-69. http://europepmc.org/articles/PMC4815242/
    [7] CHEN P, LUO X, NIE P, et al. CQ synergistically sensitizes human colorectal cancer cells to SN-38/CPT-11 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk[J]. Free Radical Biology and Medicine, 2017, 104: 280-297. doi: 10.1016/j.freeradbiomed.2017.01.033
    [8] CARDILLO T M, GOVINDAN S V, SHARKEY R M, et al. Sacituzumab govitecan (IMMU-132), an anti-trop-2/SN-38 antibody-drug conjugate: characterization and efficacy in pancreatic, gastric, and other cancers[J]. Bioconjugate Chemistry, 2015, 26(5): 919-931. doi: 10.1021/acs.bioconjchem.5b00223
    [9] BARDIA A, MAYER I A, VAHDAT L T, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer[J]. New England Journal of Medicine, 2019, 380(8): 741-751. doi: 10.1056/NEJMoa1814213
    [10] GOLDENBERG D M, SHARKEY R M. Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: a case study of anti-TROP-2 sacituzumab govitecan[J]. Taylor & Francis, 2019, 11(6): 987-995. doi: 10.1080/19420862.2019.1632115
    [11] LIU Y, XING H, WENG D, et al. Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer[J]. Cancer Letters, 2009, 274(1): 47-53. doi: 10.1016/j.canlet.2008.08.037
    [12] OHARA T, KOBAYASHI Y, YOSHIDA A, et al. Combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer[J]. International Journal of Clinical Oncology, 2012, 18(6): 1102-1106. http://europepmc.org/abstract/MED/23095879
    [13] SHOJI T, TAKATORI E, FURUTAKE Y, et al. Phase Ⅱ clinical study of neoadjuvant chemotherapy with CDDP/CPT-11 regimen in combination with radical hysterectomy for cervical cancer with a bulky mass[J]. International Journal of Clinical Oncology, 2016, 21(6): 1120-1127. doi: 10.1007/s10147-016-1008-7
    [14] CHEN Y B, SONG Y C, DU W, et al. Tumor-associated macrophages: an accomplice in solid tumor progression[J]. Journal of Biomedical Science, 2019, 26(1): 1-13. doi: 10.1186/s12929-018-0495-4
    [15] HU H, TU W, CHEN Y, et al. The combination of PKM2 overexpression and M2 macrophages infiltration confers a poor prognosis for PDAC patients[J]. Journal of Cancer, 2020, 11(8): 2022-2031. doi: 10.7150/jca.38981
    [16] JIN J Y, WANG Y, MA Q L, et al. LAIR-1 activation inhibits inflammatory macrophage phenotype in vitro[J]. Cellular Immunology, 2018, 331(1): 78-84. http://www.sciencedirect.com/science/article/pii/S0008874918302508
    [17] 邹争志, 聂培培, 倪艺榕, 等. 硫链丝菌素诱导非小细胞肺癌细胞自噬性死亡[J]. 激光生物学报, 2014, 23(1): 33-37. doi: 10.3969/j.issn.1007-7146.2014.01.006

    ZOU Z Z, NIE P P, NI Y R, et al. Thiostrepton induces autophagic cell death in non-small-cell lung cancer cells[J]. Acta Laser Biology Sinica, 2014, 23(1): 33-37. doi: 10.3969/j.issn.1007-7146.2014.01.006
    [18] YANG W, SOARES J, GRENINGER P, et al. Genomics of drug sensitivity in cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells[J]. Nucleic Acids Research, 2013, 41(1): 955-961. http://www.tandfonline.com/servlet/linkout?suffix=CIT0012&dbid=8&doi=10.1080%2F17460441.2018.1437136&key=23180760
    [19] 彭程, 薛海军, 常晓晓, 等. 不同品种黄皮果汁的品质及抗氧化能力[J]. 华南师范大学学报(自然科学版), 2020, 52(1): 70-76. doi: 10.6054/j.jscnun.2020011

    PENG C, XUE H J, CHANG X X, et al. The quality and antioxidant capacity of fruit Juice of different wampee cultivars[J]. Journal of South China Normal University (Natural Science Edition), 2020, 52(1): 70-76. doi: 10.6054/j.jscnun.2020011
    [20] QIAO J H, CHEN Y B, MI Y J, et al. Macrophages confer resistance to BET inhibition in triple-negative breast cancer by upregulating IKBKE[J]. Biochemical Pharmacology, 2020, 10(180): 114-126. http://www.sciencedirect.com/science/article/pii/S0006295220303622
    [21] PATHRIA P, JUDITH A, VARNER J A, et al. Targeting tumor-associated macrophages in cancer[J]. Trends in Immunology, 2019, 40(4): 310-327. doi: 10.1016/j.it.2019.02.003
    [22] WANG Q, STEGER A, MAHNER S, et al. The formation and therapeutic update of tumor-associated macrophages in cervical cancer[J]. International Journal of Molecular Sciences, 2019, 20(13): 1059-1069.
    [23] BAHRAMI A, HASANZADEH M, HASSANIAN S M, et al. The potential value of the PI3K/Akt/mTOR signaling pathway for assessing prognosis in cervical cancer and as a target for therapy[J]. Journal of Cellular Biochemistry, 2017, 118(12): 4163-4169. doi: 10.1002/jcb.26118
    [24] DAI B, YU R, FAN M, et al. HMQ-T-F2 suppresses migration of the human cervical cancer HeLa cells by reversing EMT via the PI3K/Akt signaling pathway[J]. Oncology Reports, 2019, 42(4): 1451-1458. http://www.researchgate.net/publication/334637080_HMQ-T-F2_suppresses_migration_of_the_human_cervical_cancer_HeLa_cells_by_reversing_EMT_via_the_PI3KAkt_signaling_pathway
    [25] D'ERRICO G, ALONSO N M, MIREIA V, et al. Tumor-associated macrophage-secreted 14-3-3ζ signals via AXL to promote pancreatic cancer chemoresistance[J]. Oncogene, 2019, 38(27): 5469-5485. doi: 10.1038/s41388-019-0803-9
    [26] LI D, JI H, NIU X, et al. Tumor-associated macrophages secrete CC-chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer[J]. Cancer Science, 2020, 111(1): 47-58. doi: 10.1111/cas.14230
    [27] WEI C, YANG C, WANG S, et al. M2 macrophages confer resistance to 5-fluorouracil in colorectal cancer through the activation of CCL22/PI3K/AKT signaling[J]. OncoTargets and Therapy, 2019, 12(1): 3051-3063. http://www.researchgate.net/publication/332487487_M2_macrophages_confer_resistance_to_5-fluorouracil_in_colorectal_cancer_through_the_activation_of_CCL22PI3KAKT_signaling
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出版历程
  • 收稿日期:  2020-04-07
  • 网络出版日期:  2021-03-24
  • 刊出日期:  2021-02-25

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