WO2021237879A1 - Aitc的用途 - Google Patents

Aitc的用途 Download PDF

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WO2021237879A1
WO2021237879A1 PCT/CN2020/100373 CN2020100373W WO2021237879A1 WO 2021237879 A1 WO2021237879 A1 WO 2021237879A1 CN 2020100373 W CN2020100373 W CN 2020100373W WO 2021237879 A1 WO2021237879 A1 WO 2021237879A1
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aitc
tumor
application
cells
drugs
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PCT/CN2020/100373
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French (fr)
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徐迅迪
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中南大学湘雅二医院
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/26—Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to the field of medical technology, in particular to the use of AITC.
  • Cancer is a general term for malignant tumors. It is characterized by uncontrolled division of abnormal cells, unlimited proliferation, invasion and destruction of surrounding normal tissues. According to its tissue source, it can be divided into cancer, sarcoma, blastoma, malignant tumor and so on. Cancers from epithelial tissues; cancers from adipose tissue, fibrous tissues, muscle tissues (collectively referred to as mesenchymal tissues), and lymphoid reticular tissues; blastomas from embryonic tissues; those that are not suitable for the above names are called sarcomas Malignant tumors, such as malignant schwannoma; there are also cancers that are specifically called, such as malignant tumors of blood cells, which are also called leukemias.
  • Cancer cells metastasize through blood and lymph fluid, and can also spread directly.
  • the cause of cancer is complex.
  • the main predisposing factors are chemical carcinogens, special viruses, radiation, hormones, free radicals, etc.; genetics, diet, and psychological status are important contributing factors.
  • liver cancer ranks among the top ten malignant tumors announced by the World Health Organization and ranks third among cancer-causing diseases. There are more than 700,000 new cases of liver cancer each year, and its morbidity and mortality are on the rise.
  • the treatment of liver cancer adheres to the basic principles of comprehensive treatment, which includes hepatectomy, liver transplantation surgery, radiofrequency ablation, microwave therapy, and transarterial chemoembolization therapy. Some targeted drugs are also used clinically, such as sorafenib and so on. Although the related diagnosis and treatment have made great progress, due to the very high recurrence rate and metastasis rate, it is still a highly fatal disease.
  • the discovery of new liver cancer treatment drugs is expected to provide new ways and means for the treatment of liver cancer.
  • Allyl isothiocyanate (Allyl isothiocyanate), alias AITC, CAS NO.57-06-7, its structural formula:
  • AITC is an agonist of the TRPA1 ion channel.
  • Transient receptor potential (TRP) channels are an important superfamily of cation channels on cell membranes. TRP channels are widely distributed and have different regulation mechanisms. By sensing various internal and external stimulating cells, they participate in many life activities such as pain, taste, mechanical sensation, maintain the ion dynamic balance of the internal and external environment of the cell, regulate the function of muscle contraction, cell proliferation, cell differentiation, gene transcription, and cell Apoptosis and cell death, etc.
  • TRPA1 is a member of the TRP family, which is characterized by the presence of more than 14 ankyrin-binding repeats at its N-terminus, while other members contain 3 to 4 ankyrin-binding repeats.
  • TRPA1 is mainly distributed on the primary sensory neurons of the dorsal root nerve, trigeminal nerve and vagus nerve. However, the role of TRPA1 in primary hepatocellular carcinoma has not been studied yet.
  • the technical problem to be solved by the present invention is to provide the use of AITC.
  • AITC can reduce the tumor volume of tumor-bearing mice, inhibit the proliferation of tumor cells, and has positive significance for cancer treatment.
  • the present invention provides the application of AITC or its analogues in the preparation of drugs for inhibiting tumor cell proliferation.
  • the inhibition of tumor cell proliferation includes: inhibiting an increase in the number of cells and/or inhibiting the formation of clones.
  • the invention also provides the application of AITC or its analogues in the preparation of drugs for inhibiting tumor volume growth.
  • the invention also provides the application of AITC or its analogues in the preparation of drugs for treating tumors.
  • the tumor is a malignant tumor, selected from cancer, sarcoma and/or blastoma.
  • the site where the tumor occurs includes the head and neck, brain, thyroid, esophagus, pancreas, liver, stomach, kidney, gallbladder, colon, rectum, ovary, cervix, uterus, prostate, bladder, testis One or more of.
  • the tumor is liver cancer.
  • the liver cancer is hepatocellular carcinoma or hepatoblastoma.
  • Huh7 cells and HepG2 cells were used to verify the therapeutic effect of AITC on hepatocellular carcinoma.
  • the treatment concentration of AITC or its analogues is 50 ⁇ mol/L to 100 ⁇ mol/L.
  • the dose of AITC or its analogues is 5 mg/kg ⁇ d -1 .
  • the method of administration is intraperitoneal injection, and the injection solvent is DMSO.
  • the present invention also provides a drug for treating tumors, which includes AITC or its analogues.
  • the medicine of the present invention also includes pharmaceutically acceptable excipients.
  • the drugs of the present invention may also include other drugs with anti-tumor functions.
  • pharmaceutically acceptable excipients are flavoring agents, osmotic pressure regulators, fillers, lubricants, preservatives, suspending agents, food colors, diluents, emulsifiers, disintegrants One or a mixture of two or more of agents or plasticizers.
  • the medicine is an oral preparation or an injection.
  • the dosage forms of oral preparations are tablets, pills, oral liquids, capsules, syrups, drop pills or granules.
  • the capsule is a hard capsule or a soft capsule.
  • the tablets are oral tablets or oral tablets.
  • the oral tablet refers to a tablet for oral administration.
  • the drugs in most of these tablets are absorbed through the gastrointestinal tract to exert their effects, and the drugs in some tablets act locally in the gastrointestinal tract.
  • oral tablets are ordinary compressed tablets, dispersible tablets, effervescent tablets, chewable tablets, coated tablets or sustained and controlled release tablets.
  • the injection preparations include injection powder injections or injection solutions.
  • the present invention also provides a method for treating tumors, which comprises administering AITC or its analogues.
  • the AITC analogs are pharmaceutically acceptable salts, solvates, hydrates, stereoisomers or clathrates of AITC.
  • the medicament of the present invention can be used in combination therapy, that is, combined application with one or more other drugs, wherein the combined application includes AITC and other drugs administered together or sequentially.
  • the other agent may be administered before, during, or after the administration of AITC or its analog.
  • the mode of administration may be the same or different.
  • AITC and other agents may be both administered in the form of injection, or both may be administered in the form of oral administration, or one may be administered in the form of injection and the other may be administered in the form of oral administration.
  • the present invention proves through experiments that AITC can significantly reduce the tumor volume of tumor-bearing mice, inhibit the proliferation of tumor cells, and has positive significance for the treatment of cancer. Therefore, the present invention provides the application of AITC in the preparation of anti-tumor drugs, and provides an anti-tumor drug containing AITC. Specifically, the application of AITC in the preparation of drugs for the treatment of liver cancer is provided. Studies have shown that for tumor-bearing animals, the subcutaneous tumor volume of AITC intervention is significantly smaller than that of the control group, and the difference is statistically significant (p ⁇ 0.01).
  • Figure 1 shows the results of plate cloning experiments; where A shows the clone formation of HepG2 cells in each group; B shows the clone formation rate of HepG2 cells in each group; C shows the clone formation of Huh7 cells in each group; D shows the clone formation of Huh7 cells in each group Clone formation rate
  • Figure 2 shows AITC's intervention in the proliferation of liver cancer cells, where A shows AITC's intervention in HepG2 cells; B shows AITC's intervention in Huh7 cells;
  • Figure 3 shows the results of the mouse subcutaneous tumor experiment, where A shows the morphology of the two groups of mice, the upper 4 are control mice, and the lower 4 are AITC test mice; B is the control group (top) and administration AITC intervention (bottom) tumor body; C shows the curve of tumor volume change in the two groups of mice with time as the abscissa.
  • the present invention provides the use of AITC, and those skilled in the art can learn from the content of this article and appropriately improve the process parameters to achieve it.
  • AITC artificial-to-everything
  • all similar replacements and modifications are obvious to those skilled in the art, and they are all deemed to be included in the present invention.
  • the method and application of the present invention have been described through preferred embodiments. It is obvious that relevant personnel can make changes or appropriate changes and combinations to the methods and applications herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention.
  • Invent technology is obvious that relevant personnel can make changes or appropriate changes and combinations to the methods and applications herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention.
  • test materials used in the present invention are all common commercially available products, all of which can be purchased in the market.
  • NOD/SCID non-obese diabetic/severe combined immunodeficiency mice
  • Liver cancer cell lines HepG2 and Huh7 were purchased from the Cell Bank of Shanghai Institute of Biological Sciences, Chinese Academy of Sciences;
  • TRPA1 agonist AITC Allyl isothiocyanate (Cat. No. 36682) was purchased from Sigma;
  • DMSO DMSO, purchased from Sigma; V900090-500ML; purity 99%;
  • Vernier caliper produced by Guanglu Measuring Tool Factory, 0-150mm electronic digital display
  • the DMEM complete medium containing 10% fetal bovine serum was used to prepare drugs with different concentration gradients, each group had 3 re-wells, and the agonist AITC concentration was 50 ⁇ M and 100 ⁇ M, respectively.
  • Gently aspirate the medium on the 6-well plate add the corresponding concentration of the drug, and place it in a cell incubator at 37°C, 5% CO 2 and saturated humidity for 1 to 2 weeks;
  • FIG. 1 A and B in Figure 1 show that, compared with the control group, AITC can significantly inhibit the cloning rate of HepG2 liver cancer cells, where P ⁇ 0.01.
  • FIG 1 C, D, AITC can significantly inhibit the colony formation rate of Huh7 liver cancer cells, where P ⁇ 0.01.
  • Hepatocarcinoma cells HepG2 and Huh7 were seeded in 96-well plates at 5 ⁇ 10 3 cells/well, and AITC of different concentrations was used to intervene for 24, 48, and 72 hours. Next, add 20 ⁇ L of MTT to each well, continue to incubate for 4h, replace with 150 ⁇ L of DMSO, and shake for 10 minutes. The absorbance measurement was performed at a wavelength of 490nm.
  • hepatoma cell line HepG2 cells 5 ⁇ 10 6 hepatoma cell line HepG2 cells were respectively injected into the right side of NOD/SCID (8 in total), and reared according to the stated standards. Vernier caliper subcutaneous tumors were measured path length, a formula 1/2 ⁇ length ⁇ width 2 determines the size of the tumor, when the tumor is formed to a volume of approximately 100mm 3 mice were randomized into when the treatment intervention group and control group, each of 4 per group .
  • Treatment intervention group Treatment intervention group:
  • DMSO solvent was injected into the abdominal cavity at a dose of 5 ⁇ l/(kg body weight), once a day.

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Abstract

AITC在制备治疗抗肿瘤的药物中的应用，并提供了一种含有AITC的抗肿瘤药物。具体的，提供了AITC在制备治疗肝癌的药物中的应用。研究表明，对于荷瘤动物而言，AITC干预的皮下瘤体积明显小于对照组（control），差异有统计学意义(p＜0.01)。实验证明，AITC能够显著降低荷瘤小鼠的肿瘤体积、抑制肿瘤细胞的增殖，对癌症的治疗存在积极意义。

Description

AITC的用途
本申请要求于2020年05月26日提交中国专利局、申请号为202010454911.7、发明名称为“AITC的用途”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及医药技术领域，尤其涉及AITC的用途。
背景技术
癌症是恶性肿瘤的统称。特点为不正常细胞失控分裂、无限增殖、侵入并破坏周围正常组织。按其组织来源可分为癌、肉瘤、母细胞瘤、恶性瘤等。来自上皮组织的称做癌；起源于脂肪组织、纤维组织、肌肉组织(统称间叶组织)及淋巴网状组织的称为肉瘤；来源于胚胎组织的称母细胞瘤；不宜用以上名称的叫恶性瘤，如恶性神经鞘瘤；还有些特殊称呼的癌症，如血液细胞的恶性肿瘤也称做白血病。癌症细胞经血液和淋巴液转移，也可直接蔓延。癌症的病因复杂，主要诱发因素有化学致癌物、特殊的病毒、射线、激素、自由基等；遗传、饮食、心理状态是重要的促进因素。
原发性肝癌在世界卫生组织公布的恶性肿瘤排名前十，在癌致死疾病中高居第三位。每年新发肝癌病例数超过70万，且其发病率及死亡率呈现上升趋势。肝癌治疗的秉承综合治疗的基本原则，其包括肝切除术、肝移植手术的外科手术，射频消融、微波治疗及经动脉化学栓塞治疗的介入治疗等。一些靶向药物也应用于临床，如索拉菲尼等。尽管相关的诊治取得了很大的进步，但是由于复发率及转移率非常高，使它仍是一种高致死性疾病。新肝癌治疗药物的发现有望为肝癌的治疗提供新的途径和手段。
异硫氰酸烯丙酯，(Allyl isothiocyanate)，别名AITC，CAS NO.57-06-7，其结构式：
Figure PCTCN2020100373-appb-000001
AITC为TRPA1离子通道的激动剂。瞬时受体电位(TRP)通道是细胞膜上一类重要的阳离子通道超家族。TRP通道分布广泛，具有不同的调节机制。通过感知各种内外刺激细胞，它们参与许多生命活动如痛觉、味觉、机械的感觉，维持细胞的内部和外部环境的离子动态平衡，调节肌肉收缩的功能，细胞增殖，细胞分化，基因转录，细胞凋亡和细胞死亡等。TRPA1是TRP家族中的一员，其特点是其N端存在14个以上与锚蛋白结合的重复序列，而其他成员含有3至4个锚蛋白结合重复序列。TRPA1主要分布于背根神经、三叉神经和迷走神经的初级感觉神经元上。但TRPA1在原发性肝细胞癌中的作用尚无人研究。
发明内容
有鉴于此，本发明要解决的技术问题在于提供AITC的用途，研究表明，AITC能够降低荷瘤小鼠的肿瘤体积、抑制肿瘤细胞的增殖，对癌症的治疗存在积极意义。
本发明提供了AITC或其类似物在制备抑制肿瘤细胞增殖的药物中的应用。
在本发明实施例中，所述抑制肿瘤细胞增殖包括：抑制细胞数量的增加和/或抑制克隆的形成。
本发明还提供了AITC或其类似物在制备抑制肿瘤体积增长的药物中的应用。
本发明还提供了AITC或其类似物在制备治疗肿瘤的药物中的应用。
一些实施例中，所述肿瘤为恶性肿瘤，选自癌、肉瘤和/或母细胞瘤。
一些实施例中，所述肿瘤发生的部位包括头颈部、脑部、甲状腺、食管、胰腺、肝脏、胃、肾脏、胆囊、结肠、直肠、卵巢、子宫颈、子宫、前列腺、膀胱、睾丸中的一种或多种。
一些具体实施例中，所述肿瘤为肝癌。
一些具体实施例中，所述肝癌为肝细胞肝癌或肝母细胞瘤。
在具体实施例中，以Huh7细胞和HepG2细胞验证AITC对肝细胞肝癌的治疗作用。
在本发明中，对于细胞实验，AITC或其类似物的处理浓度为50μmol/L～100μmol/L。对于动物实验，AITC或其类似物的剂量为5mg/kg·d -1。给予方式为腹腔注射，注射的溶剂为DMSO。
本发明还提供了一种治疗肿瘤的药物，其包括AITC或其类似物。
本发明所述的药物中，还包括药学上可接受的辅料。
本发明所述的药物中，还可以包括其他具有抗肿瘤功能的药物。
在本发明提供的一些实施例中，药学上可接受的辅料为矫味剂、渗透压调节剂、填充剂、润滑剂、防腐剂、助悬剂、食用色素、稀释剂、乳化剂、崩解剂或增塑剂中的一种或两者以上的混合物。
作为优选，所述药物为口服制剂或注射用剂。其中口服制剂的剂型为片剂、丸剂、口服液剂、胶囊剂、糖浆剂、滴丸剂或颗粒剂。优选的，胶囊剂为硬胶囊剂或软胶囊剂。片剂为口服片剂或口腔片剂。所述口服片剂指供口服的片剂，多数此类片剂中的药物是经胃肠道吸收而发挥作用，也有的片剂中的药物是在胃肠道局部发挥作用。在本发明提供的一些实施例中，口服片剂为普通压制片、分散片、泡腾片、咀嚼片、包衣片或缓控释片。所述注射用剂包括注射粉针剂或注射液。
本发明还提供了一种治疗肿瘤的方法，其包括给予AITC或其类似物。
本发明中，所述AITC的类似物为AITC的可药用的盐、溶剂化物、水合物、立体异构体或包合物。
本发明所述的药物可在联合治疗中使用，即与一种或多种其它药剂联合应用，其中所述联合应用包括AITC与其它药剂一起施用，或者依次施用。例如，所述其它药剂可在施用AITC或其类似物之前、期间或之后施用。施用的方式可相同也可不同，例如AITC与其它药剂可皆以注射形式给予，也可皆通过口服形式给予，也可一者通过注射形式给予另一者通过口服形式给予。
本发明通过实验证明，AITC能够显著降低荷瘤小鼠的肿瘤体积、抑制肿瘤细胞的增殖，对癌症的治疗存在积极意义。因此，本发明提供了AITC在制备治疗抗肿瘤的药物中的应用，并提供了一种含有AITC的抗 肿瘤药物。具体的，提供了AITC在制备治疗肝癌的药物中的应用。研究表明，对于荷瘤动物而言，AITC干预的皮下瘤体积明显小于对照组(control)组，差异有统计学意义(p＜0.01)。
附图说明
图1示平板克隆实验结果；其中，A示各组HepG2细胞的克隆形成情况；B示各组HepG2细胞的克隆形成率；C示各组Huh7细胞的克隆形成情况；D示各组Huh7细胞的克隆形成率；
图2示AITC干预肝癌细胞的增殖能力，其中A示AITC干预HepG2细胞；B示AITC干预Huh7细胞；
图3示小鼠皮下瘤实验结果，其中，A示两组小鼠的形态，上面4只为对照组小鼠，下面四只为AITC受试小鼠；B示对照组组(上)和给予AITC干预(下)的瘤体；C示以时间为横坐标两组小鼠瘤体积变化的曲线。
具体实施方式
本发明提供了AITC的用途，本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。
本发明采用的试材皆为普通市售品，皆可于市场购得。
雌性四周龄NOD/SCID(非肥胖型糖尿病/重症联合免疫缺陷小鼠)，购自于北京维通利华公司，所有小鼠均喂养在中南大学湘雅二医院实验动物中心SPF级别小鼠饲养间内，环境温度稳定于18～22℃之间，湿度控制在50％～60％之间。NOD/SCID小鼠喂养于无毒无特异病原体的塑料鼠盒内，用标准颗粒饲料以及纯净水饲养并保持其昼夜12小时节律，所需环境都满足国家实验动物管理和使用指南要求，所有操作都得到中南大学湘雅二医院动物伦理委员会批准及监督；
肝癌细胞株HepG2，Huh7购自中国科学院上海生命科学院细胞库；
TRPA1激动剂AITC：异硫氰酸烯丙酯(货号：36682)购自Sigma公司，；
DMSO，购自Sigma公司；V900090-500ML；纯度99％；
游标卡尺，广陆量具厂生产，0-150mm电子数显；
Varioskan Flash多功能酶标仪，Thermo。
下面结合实施例，进一步阐述本发明：
实施例1平板细胞克隆形成实验
I.克隆形成率试验
1、第1天分别取对数生长期的HepG2、Huh7肝癌细胞，用0.25％胰蛋白酶消化并吹打成单个细胞，完成细胞计数；
2、将细胞悬液于10％胎牛血清的DMEM完全培养基中混匀，调整细胞密度，将每组细胞分别以每孔2ml培养基、1500个细胞/孔密度分别接种于6孔板中，并轻轻转动，使细胞分散均匀，置于含5％CO 2的37℃培养箱中培养过夜；
3、第2上午根据实验设计用含10％胎牛血清的DMEM完全培养基配制所需不同浓度梯度的药物，每组浓度3个复孔，激动剂AITC浓度分别50μM、100μM。轻柔地将6孔板上层培养基吸出，加入相应浓度药物，置于37℃，5％CO 2及饱和湿度的细胞培养箱中培养1～2周；
4、经常观察，当培养皿中出现肉眼可见的克隆时，终止培养。弃去上清液，用PBS小心浸洗2次，加4％多聚甲醛2mL固定细胞15分钟。然后去固定液，加适量0.5％结晶紫染色液染10～15分钟，然后用清水缓慢洗去染色液，空气干燥，计数拍照。
5、将6孔板底部叠加一张带网格的透明胶片，用肉眼直接计数克隆，计数大于50个细胞的克隆数。最后计算克隆形成率。
克隆形成率＝(克隆数/接种细胞数)×100％
结果如图1。图1中A、B显示，相比于对照组，AITC可以显著抑制HepG2肝癌细胞的克隆形成率，其中P＜0.01。图1中C、D，AITC 可以显著抑制Huh7肝癌细胞的克隆形成率，其中P＜0.01。
实施例2：MTT实验
肝癌细胞HepG2和Huh7以5×10 3细胞/孔种板于96孔板，用不同浓度的AITC干预24、48、72h。接下来，20μL MTT添加到每个孔，继续孵育4h后置换成150μL DMSO，振荡10分钟。以490nm波长进行吸光度测量。
如图2A、2B所示，分别以50uM和100uM的AITC干预肝癌细胞HepG2和Huh7，肝癌细胞的增殖能力与对照组比较明显降低，差异有统计学意义(**代表P＜0.001，***代表P＜0.0001)。
实施例3皮下瘤模型试验
将5×10 6个肝癌细胞株HepG2细胞分别注射至NOD/SCID(共8只)的右侧颈背部，按照所述标准进行饲养。游标卡尺分别测量皮下肿瘤的长短径，以公式1/2×长度×宽度 2确定肿瘤大小，当肿瘤形成至体积约100mm 3时将小鼠随机分为对照组和治疗干预组，每组各4只。
治疗干预组：
将50mg AITC溶解于50mL DMSO中，以形成注射药物，浓度为1μg/μL，用该组小鼠进行腹腔内注射，剂量为5mg/(kg体重)，1次/天。
对照组：
于腹腔内注射DMSO溶剂，剂量5μl/(kg体重)，1次/天。
肿瘤大小以体积＝1/2×长度×宽度2检测。在第32天将小鼠处死，比较生存率和肿瘤体积大小。
结果如图3：如图可见，相对于对照组而言，AITC干预可以显著抑制皮下瘤生长，P＜0.01。
以上仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。

Claims (10)

  1. AITC或其类似物在制备抑制肿瘤细胞增殖的药物中的应用。
  2. 根据权利要求1所述的应用，其特征在于，所述抑制肿瘤细胞增殖包括：抑制细胞数量的增加和/或抑制克隆的形成。
  3. AITC或其类似物在制备抑制肿瘤体积增长的药物中的应用。
  4. AITC或其类似物在制备治疗肿瘤的药物中的应用。
  5. 根据权利要求1～4任一项所述的应用，其特征在于，所述肿瘤为恶性肿瘤，选自癌、肉瘤和/或母细胞瘤。
  6. 根据权利要求5所述的应用，其特征在于，所述肿瘤发生的部位包括头颈部、脑部、甲状腺、食管、胰腺、肝脏、胃、肾脏、胆囊、结肠、直肠、卵巢、子宫颈、子宫、前列腺、膀胱、睾丸中的一种或多种。
  7. 根据权利要求1～7任一项所述的应用，其特征在于，所述肿瘤为肝癌。
  8. 根据权利要求7所述的应用，其特征在于，所述肝癌为肝细胞肝癌或肝母细胞瘤。
  9. 根据权利要求1～8任一项所述的应用，其特征在于，AITC或其类似物的剂量为5mg/kg·d -1。
  10. 一种治疗肿瘤的药物，其特征在于，包括AITC或其类似物。
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