List of Common in Vivo Tumor Models

Medicilon Animal in vivo Tumor Models

In vivo Tumor models can be divided into three categories:
Animal model of spontaneous tumor
Induced tumor animal model
Transplantation tumor animal model

1.Spontaneous tumor animal model: without human treatment; naturally occurring

Overall evaluation of spontaneous tumors-The etiology of spontaneous tumors in animals is often determined by the genetic characteristics of the animal, which is far away from the cause of human cancer. The growth rate of tumors varies greatly among animals, and it is difficult to obtain a large number of tumor-bearing animals within a limited time. Therefore, animal models of spontaneous tumors are rarely widely used in routine screening of anti-tumor drugs.

2.Animal model of induced tumor: under experimental conditions; use of carcinogens induce tumors in animals

(animal model of induced tumor) refers to an animal model that uses carcinogens to induce animal tumors under experimental conditions. It is a common method for experimental oncology research. Commonly used to verify the role of suspicious carcinogens, it is also increasingly used in the study of tumorigenesis mechanisms and the observation of prevention and treatment effects. It has an important position in the research of tumor etiology, genetics, and biology. Since the inducing factors and conditions can be artificially controlled, the inducing rate is much higher than the natural incidence rate, so it is superior to spontaneous tumors in tumor experimental research.

There are many types of animals used to induce experimental tumors, and they have different responses to the same carcinogenic factors due to different races. Commonly used animals are mainly mammals, among which rodents are the most used and most widely used, including various rats, mice, guinea pigs and so on.

The principle of the inducible tumor model is to use exogenous carcinogenic factors to cause abnormal genetic characteristics of the cell, showing abnormal growth and high proliferation activity, forming a tumor. The carcinogenic factors are mainly chemical, physical and biological carcinogens, and chemical carcinogens are the most common. There are more than one thousand species known, and there are many types used to induce experimental tumors, such as Benzopyrene, methylcholanthracene, benzidine, nitrosamines, aflatoxins. The carcinogenic intensity and carcinogenic spectrum of various carcinogens vary greatly, and the location or type of tumors caused by the administration of the same carcinogen through different routes can be very different. Some chemical carcinogens have obvious organophilic or tissue characteristics. Therefore, appropriate carcinogens and carcinogenic pathways should be selected according to the needs in the experimental work, and other influencing factors or experimental conditions should be determined.

Basic principle: the use of exogenous carcinogens to cause changes in the genetic characteristics of cells, resulting in abnormal growth and highly proliferating active cells to form tumors. Exogenous carcinogens are mainly chemical, physical (such as radioactive materials) and biological (such as viruses that induce animal tumors), of which chemical carcinogens are the most commonly used.

①Basic method of induced tumor animal model: During the experiment, it is necessary to pay attention to choose the appropriate carcinogenic method, animal germline, carcinogen and its solvent, dose, route and observation time. The dose of carcinogen should ensure a higher survival rate, shorter induction period and higher induction tumor frequency.
Commonly used methods and routes of carcinogen administration:
 a. Smearing method: smear on the back and ear skin, mainly used to induce skin tumors.
 b. Oral administration method: through drinking water, feed or feeding animals. Commonly used for esophageal cancer, gastric cancer and colorectal cancer.
 c. Injection method: The carcinogen is made into a solution and injected into the body through subcutaneous, intramuscular, intravenous or body cavity, etc. This method is more commonly used.
 d. Tracheal injection method: commonly used to induce lung cancer.
 e. Threading method: Place the carcinogen in a sterile test tube, heat it to liquefy it, adsorb it on the prefabricated thread knot, and then thread this thread knot into the target tissue to induce tumors.
 f. Burial method: embedded under the skin or other tissues.

② Animals and carcinogens of induced tumor models
Animals: rats, mice, dogs, etc.
Carcinogens: polycyclic hydrocarbons, nitrosamines, azos, and aflatoxin (0.001-0.015ppm aflatoxin B1 in feed, fed for 6 months, induced liver cancer in rats).

Overall evaluation of induced tumor models: About 80% of human cancers are caused by environmental factors. The etiology of induced tumors is similar to that of human cancers, and they all form tumors after a long evolutionary process. Animal-induced tumors are animal models that are more similar to human tumors. However, the cause of human cancer is very complicated, and it is often not caused by known animal carcinogens. In addition, the histopathological type, occurrence and development of animal-induced tumors may not be completely consistent with human cancer.

The biggest difficulty of this model is that the cancer induction time is long, the cancer formation rate is often less than 100%, and the individual tumor occurrence time and development rate between animals vary greatly, making it difficult to use untreated animals as a control for treated animals.

3.Animal model of transplanted tumor

The animal model of transplantable tumor refers to the tumor formed by continuous passage of animal or human tumors into the same or heterogeneous animals.
This experimental method is the most commonly used in vivo method for screening antitumor drugs and has an important role. At present, most of the commonly used antitumor drugs in clinic are first discovered through this experimental method.

The test drugs are generally given for 7-10 days, and the animals can be dissected on the 8-11 days to obtain the results. Through the observation of some indicators, it can be judged whether the test drug has the effect of inhibiting tumor growth. This is irreplaceable by any in vitro test, and the results can provide an important basis for the efficacy of anticancer drugs.
It is easier to implement than the aforementioned spontaneous and induced animal tumors. The success rate of existing transplanted tumor vaccination can reach 100%, and a large number of tumors (tens to hundreds of animals) with fairly uniform growth can be obtained at the same time.
①, the choice of animals
Animals commonly used for transplanted tumors are mice, rats and hamsters. The anti-tumor effect of the research drug can be selected from three or more transplanted tumors of mice and rats for experimental treatment; when screening anti-tumor drugs, the source of each batch of animals should be the same;
Choose inbred, outbred or F1 animals according to the characteristics of the tumor strain; both male and female animals can be used (female animals such as breast cancer must be used).
 ▲Each batch of experiments only use animals of the same sex.
 ▲Mice weigh 18~22g, rats weigh 50~70g
 ▲At least 10 animals in each group, 5 to 10 nude mice can be used.
②, the selection of tumor cells
  The replication of transplanted tumor models requires the use of tumor cell lines (tumor strains) or cell lines (cell lines).
  Cell strain refers to a population of cells with special genetic, biochemical properties, or specific markers obtained from primary cultures or cell lines by selection or cloning methods.
  The histological type and growth characteristics of the tumor strains tend to be stable, and can be transplanted in the same line, same species or heterogeneous animals and serially passaged.
  Growth characteristics, including inoculation survival rate, growth rate, auto-regression rate, host lifespan and host response, etc.
  Cell line: The primary culture is a cell line after the first pass, and consists of the cell lineage that originally existed in the primary culture.

③、Inoculation method
  (1) General requirements
  The entire operation should be carried out under sterile conditions, and can be operated in a sterile room and an ultra-clean workbench. After the animals are sacrificed, the skin should be disinfected. Each solid tumor should be cut with a sterilized surgical instrument, and the ascites tumor should be sucked with a sterilized syringe.
  Contamination of the tumor mass is often the main reason for the failure of vaccination, and special attention should be paid!! When operating in the hot season, ice cubes can be placed around the vessel containing the tumor source to directly cool down.
  Common inoculation sites:
  Solid tumor _ subcutaneous armpit   Muscle vaccination thigh muscles
  Ascites tumor _ abdominal cavity

④, cryopreservation and recovery of tumor cells
In order to enable long-term use of tumor cells, prevent degradation or mutation, and preserve the characteristics of different generations of cells, it is necessary to cryopreserve tumor cells or tumor strains. Generally stored in liquid nitrogen for 1 to 2 years, the cell survival rate can reach 80% to 90%.

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