抗寄生虫药物治疗恶性肿瘤的相关研究进展

杨柳; 周诗婕; 高文仓

doi:10.16766/j.cnki.issn.1674-4152.004014

抗寄生虫药物治疗恶性肿瘤的相关研究进展

doi: 10.16766/j.cnki.issn.1674-4152.004014

1.
浙江中医药大学第二临床医学院，浙江杭州 310053
2.
浙江中医药大学附属第二医院肿瘤内科，浙江杭州 310005

基金项目:

“白求恩·肿瘤临床研究计划”项目 BCF-XD-ZL-20220118-032

浙江省中医药科技计划项目 2021ZB127

浙江省中医药科技计划项目 2018ZB064

详细信息

通讯作者:
高文仓，E-mail：yl18058746290@163.com

中图分类号: R730.5 R978.6
计量
- 文章访问数: 8
- HTML全文浏览量: 4
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2024-09-25
- 网络出版日期: 2025-08-14

Research progress of antiparasitic drugs for malignant tumor treatment

1.
The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, China

摘要

摘要: 恶性肿瘤是世界范围内威胁人类寿命和健康的元凶之一。肿瘤广泛转移引起的多器官衰竭、继发感染、大出血以及免疫系统的抑制导致恶性肿瘤的死亡率高居第2位。现阶段恶性肿瘤的治疗模式以传统的手术治疗、化学治疗、放射治疗为主，辅以新型的免疫治疗、靶向治疗，存在着治疗不彻底、易转移和复发、不良反应多等缺点。寄生虫类疾病同样是严重危害人类健康的疾病，具有严重破坏性且十分普遍的传染性，每年造成数百万人发病和死亡，其中以蛔虫、弓形虫和蠕虫感染较为多见。据报道，全球约70%的人口曾感染蛔虫；约30%~50%的人口曾感染弓形虫；约16%的人口曾感染蠕虫。寄生虫进入人体后进一步感染呼吸系统、消化系统甚至神经系统，严重时引起脑膜炎、心肌炎等并发症，导致器官功能衰竭甚至死亡。近年来，随着对寄生虫相关疾病研究的不断深入，已经证实寄生虫感染与恶性肿瘤发生、发展之间存在着密切关系。寄生虫可以通过直接感染和间接诱导促进恶性肿瘤的发生、进展、转移。基于此，国内外学者对抗寄生虫药物的抗肿瘤特性进行了广泛研究，抗寄生虫药物有望实现“再利用”，作为恶性肿瘤的新型治疗手段用于临床。本文总结了近年来抗寄生虫药物治疗恶性肿瘤的相关研究进展，旨在为恶性肿瘤提供更多安全有效的治疗方案。
- 抗寄生虫药物 /
- 恶性肿瘤 /
- 作用机制 /
- 药物再利用
Abstract: Malignant tumors are one of the culprits threatening human lifespan and health worldwide. The mortality rate of malignant tumors ranks second due to multiple organ failure, secondary infections, massive bleeding, and immune system suppression caused by widespread tumor metastasis. At present, the treatment mode of malignant tumors mainly relies on traditional surgical treatment, chemotherapy, and radiation therapy, supplemented by newer types such as immunotherapy and targeted therapy. However, there are disadvantages such as incomplete tumor eradication, high risk metastasis and recurrence, and multiple adverse reactions. Parasitic diseases are also serious threats to human health, with severe destructive and widespread infectivity, causing millions of illnesses and deaths every year. Common parasitic infections include roundworm, Toxoplasma gondii, and other helminths. According to reports, about 70% of the global population has been infected with roundworms, about 30%-50% with Toxoplasma gondii, about 16% with other parasitic worms. Once inside the human body, parasites can spread to the respiratory, digestive, and even nervous systems, potentially cause complications such as meningitis and myocarditis, which may lead to organ failure and even death. In recent years, extensive research on parasitic diseases has confirmed a strong relationship between parasitic infections and the occurrence and development of malignant tumors. Parasites can promote the occurrence, progression, and metastasis of malignant tumors through direct both infection and indirect induction. Based on this, scholars worldwide have conducted extensive research on the anti-tumor properties of antiparasitic drugs. These antiparasitic drugs are expected to be promising for malignant tumors for clinical use. This article summarizes the research progress of antiparasitic drugs in the treatment of malignant tumors in recent years, aiming to provide safer and more effective treatment options for malignant tumors.
- Antiparasitic drug /
- Malignant tumor /
- Action mechanism /
- Drug reuse

HTML全文

参考文献(35)

[1]	HE W, LI Q, LU Y, et al. Cancer treatment evolution from traditional methods to stem cells and gene therapy[J]. Curr Gene Ther, 2022, 22(5): 368-385.
[2]	杨茜云, 沈国强. 弓形虫感染与肿瘤的关系研究进展[J]. 中国热带医学, 2021, 21(12): 1201-1205. YANG Q Y, SHEN G Q. The interplay between toxoplasma gondii infections and tumors[J]. China Tropical Medicine, 2021, 21(12): 1201-1205.
[3]	刘舒, 李抒凝, 陈晶. 虫类中药在肿瘤治疗中的机制研究进展[J]. 环球中医药, 2022, 15(7): 1286-1290. doi: 10.3969/j.issn.1674-1749.2022.07.038 LIU S, LI S N, CHEN J. Research progress on the mechanism of insect Chinese medicine in cancer treatment[J]. Global Traditional Chinese Medicine, 2022, 15(7): 1286-1290. doi: 10.3969/j.issn.1674-1749.2022.07.038
[4]	何晴, 吴银娟, 殷颖璇, 等. 抗寄生虫药物在抗恶性肿瘤中的作用研究进展[J]. 热带医学杂志, 2021, 21(10): 1361-1363. doi: 10.3969/j.issn.1672-3619.2021.10.029 HE Q, WU Y J, YIN Y X, et al. Advances on anti-malignant tumor effect of anti-parasitic drugs[J]. Journal of Tropical Medicine, 2021, 21(10): 1361-1363. doi: 10.3969/j.issn.1672-3619.2021.10.029
[5]	吴银娟, 何晴, 殷颖璇, 等. 蠕虫感染与肿瘤发生关系的研究进展[J]. 传染病信息, 2022, 35(1): 84-89. doi: 10.3969/j.issn.1007-8134.2022.01.012 WU Y J, HE Q, YIN Y X, et al. Research progress on the relationship between helminth infection and tumorigenesis[J]. Infectious Disease Information, 2022, 35(1): 84-89. doi: 10.3969/j.issn.1007-8134.2022.01.012
[6]	DHEILLY N M, EWALD P W, BRINDLEY P J, et al. Parasite-microbe-host interactions and cancer risk[J]. PLoS Pathog, 2019, 15(8): 1-10.
[7]	李刚, 彭飞, 詹麒, 等. 华支睾吸虫感染背景的肝细胞癌影像组学特征及预测华支睾吸虫感染的性能评价[J]. 中国病原生物学杂志, 2024, 19(9): 1042-1046. LI G, PENG F, ZHAN Q, et al. Imaging omics characteristics of hepatocellular carcinoma with background of Clonorchis sinensis infection and performance evaluation for predicting C. sinensis infection[J]. Journal of Pathogen Biology, 2024, 19(9): 1042-1046.
[8]	SHI Y, YU K, LIANG A, et al. Identification and analysis of the tegument protein and excretory-secretory products of the carcinogenic liver fluke Clonorchis sinensis[J]. Front Microbiol, 2020, 11: 555730. DOI: 10.3389/fmicb.2020.555730.
[9]	张莹, 王玉桂, 时志琪, 等. 蠕虫感染影响宿主胆汁酸代谢的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(5): 648-652. ZHANG Y, WANG Y G, SHI Z Q, et al. Progress of researches on effects of helminth infection on bile acid metabolism[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2024, 42(5): 648-652.
[10]	HAMID H K S. Schistosoma japonicum-associated colorectal cancer: a review[J]. Am J Trop Med Hyg, 2019, 100(3): 501-505.
[11]	王小溪, 何兴, 潘卫庆. 寄生虫感染与癌症[J]. 中国热带医学, 2019, 19(4): 392-395, 400. WANG X X, HE X, PAN W Q. Parasitic infections and cancer[J]. China Tropical Medicine, 2019, 19(4): 392-395, 400.
[12]	张莹舒, 丁昕, 戴洋. 寄生虫抗癌症作用及其机制研究进展[J]. 中国血吸虫病防治杂志, 2024, 36(1): 91-97. ZHANG Y S, DING X, DAIY Y. Anticancer effect of parasites and its underlying mechanisms: a review[J]. Chinese Journal of Schistosomiasis Control, 2024, 36(1): 91-97.
[13]	吕金津, 王巍. 苯并咪唑类驱虫药抗肿瘤作用机制的研究进展[J]. 现代药物与临床, 2020, 35(5): 1045-1048. LYU J J, WANG W. Research progress on mechanism of antiparasitic medications with benzimidazolestructure in treatment of cancer[J]. Drugs & Clinic, 2020, 35(5): 1045-1048.
[14]	SHIMOMURA I, YOKOI A, KOHAMA I, et al. Drug library screen reveals benzimidazole derivatives as selective cytotoxic agents for KRAS-mutant lung cancer[J]. Cancer Lett, 2019, 451: 11-22.
[15]	BAI R Y, STAEDTKE V, APRHYS C M, et al. Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme[J]. Neuro-Oncol, 2011, 13(9): 974-982.
[16]	LIMBU K R, CHHETRI R B, OH Y S, et al. Mebendazole impedes the proliferation and migration of pancreatic cancer cells through SK1 inhibition dependent pathway[J]. Molecules, 2022, 27(23): 8127. DOI: 10.3390/molecules27238127.
[17]	DOBROSOTSKAYA I Y, HAMMER G D, SCHTEINGART D E, et al. Mebendazole monotherapy and long-term disease control in metastatic adrenocortical carcinoma[J]. Endocr Pract, 2011, 7(3): e59-62.
[18]	ELAYAPILLAI S, RAMRAJ S, BENBROOK D M, et al. Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer[J]. Gynecol Oncol, 2021, 160(1): 302-311.
[19]	WANG Z, REN J, DU J, et al. Niclosamide as a promising therapeutic player in human cancer and other diseases[J]. Int J Mol Sci, 2022, 23(24): 16116. DOI: 10.3390/ijms232416116.
[20]	BARBOSA E J, LOBENBERG R, DE ARAUJO G L B, et al. Niclosamide repositioning for treating cancer: challenges and nano-based drug delivery opportunities[J]. Eur J Pharm Biopharm, 2019, 141: 58-69.
[21]	BANSARD L, BOUVET O, MOUTIN E, et al. Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy[J]. Stem Cell Reports, 2022, 17(4): 835-848.
[22]	轩秀晨, 黄卉, 吕桂香. 氯硝柳胺的药理学作用及机制研究进展[J]. 医学综述, 2021, 27(15): 3055-3060. doi: 10.3969/j.issn.1006-2084.2021.15.027 XUAN X C, HUANG H, LYU G X. Research Progress in Pharmacological Effects and Mechanisms of Niclosamide[J]. Medical Recapitulate, 2021, 27(15): 3055-3060. doi: 10.3969/j.issn.1006-2084.2021.15.027
[23]	RAI R, DEY D K, BENBROOK D M, et al. Niclosamide causes lysosome-dependent cell death in endometrial cancer cells and tumors[J]. Biomed Pharmacother, 2023, 161: 114422. DOI: 10.1016/j.biopha.2023.114422
[24]	MATHEW M, SIVAPRAKASAM S, DHARMALINGAM-NANDAGOPAL G, et al. Induction of oxidative stress and ferroptosis in triple-negative breast cancer cells by Niclosamide via blockade of the function and expression of SLC38A5 and SLC7A11[J]. Antioxidants(Basel), 2024, 13(3): 291. DOI: 10.3390/antiox13030291.
[25]	KANG H W, KIM J H, LEE D E, et al. Combination therapy of niclosamide with gemcitabine inhibited cell proliferation and apoptosis via Wnt/β-catenin/c-Myc signaling pathway by inducing β-catenin ubiquitination in pancreatic cancer[J]. Cancer Biol Ther, 2023, 24(1): 2272334. DOI: 10.1080/15384047.2023.2272334.
[26]	SCHULTZ C W, NEVLER A. Pyrvinium pamoate: past, present, and future as an anti-cancer drug[J]. Biomedicines, 2022, 10(12): 3249. DOI: 10.3390/biomedicines10123249.
[27]	HUANG S W, SUN M T, LEE W S, et al. Cancer as an infectious disease: a different treatment alternative using a combination of tigecycline and pyrvinium pamoate: an example of breast cancer[J]. J Microbiol Immunol Infect, 2022, 55(1): 51-59.
[28]	JI Y, ZHANG W, SHEN K, et al. The ELAVL3/MYCN positive feedback loop provides a therapeutic target for neuroendocrine prostate cancer[J]. Nat Commun, 2023, 14(1): 7794. DOI: 10.1038/s41467-023-43676-3.
[29]	KIM H, JANG B, ZHANG C, et al. Targeting stem cells and dysplastic features with Dual MEK/ERK and STAT3 suppression in gastric carcinogenesis[J]. Gastroenterology, 2024, 166(1): 117-131.
[30]	郑云秋, 屈洪党, 徐志本, 等. 青蒿素对脂多糖活化的小胶质细胞炎症介质释放的影响[J]. 中华全科医学, 2019, 17(7): 1097-1100. doi: 10.16766/j.cnki.issn.1674-4152.000872 ZHENG Y Q, QU H D, XU Z B, et al. Effect of artemisinin on the release of inflammatory mediatorsof LPS-activated microglia[J]. Chinese Journal of General Practice, 2019, 17(7): 1097-1100. doi: 10.16766/j.cnki.issn.1674-4152.000872
[31]	HUANG Z, GAN S, ZHUANG X, et al. Artesunate inhibits the cell growth in colorectal cancer by promoting ROS-dependent cell senescence and autophagy[J]. Cells, 2022, 11(16): 2472. DOI: 10.3390/cells11162472.
[32]	MA Z C, CHEN W J, LIU Y D, et al. Artesunate sensitizes human hepatocellular carcinoma to sorafenib via exacerbating AFAP1L2-SRC-FUNDC1 axis-dependent mitophagy[J]. Autophagy, 2024, 20(3): 541-556.
[33]	OIEN D B, PATHOULAS C L, RAY U, et al. Repurposing quinacrine for treatment-refractory cancer[J]. Semin Cancer Biol, 2021, 68: 21-30.
[34]	JUNG D, KHURANA A, ROY D, et al. Quinacrine upregulates p21/p27 independent of p53 through autophagy-mediated downregulation of p62-Skp2 axis in ovarian cancer[J]. Sci Rep, 2018, 8(1): 2487.
[35]	SUN Q, LIU B, LAN Q, et al. Antimicrobial agent chloroxylenol targets β catenin mediated Wnt signaling and exerts anticancer activity in colorectal cancer[J]. Int J Oncol, 2023, 63(5): 121. DOI: 10.3892/ijo.2023.5569.