- Background of project (课题背景)
Cancer becomes a common disease with more and more new cases diagnosed every year. Therefore, cancer therapy is drawing increasingly attention nowadays. But there is two big problems which need to solve in progression of cancer therapy: 1) tumorrsquo;s multidrug resistance towards different kinds of chemodrugs; 2) chemodrugsrsquo; toxicity towards normal cells in body. The first problem could account for the difficulty of completely killing cancer cells and curing cancer, while the second problem could give the reason why chemotherapy has such big side effects.
Ganoderma lucidum, a kind of notable traditional Chinese medicine which is spread nationwide, has been used as a folk remedy for health improvement for a long history. As is known, it has been used for prevention and treatment of multiple diseases in China, such as cancer, neurasthenia, hepatopathy, aging, and diabetics. Now it has become a new target of cancer therapy because of its potential cytotoxicity against cancer cells with low toxicity towards other normal tissue and organs, and its potential reversal effect towards drug resistance when combined with other chemodrugs. With these advantages, it is promising to develop Ganoderma lucidum as a new dietary care strategy in combination with chemotherapy for cancer.
In order to demonstrate lingzhirsquo;s anti-cancer effect and its mechanisms, accumulated researches have been done and statistics have shown that some specific compounds extracted from Ganoderma exhibit a broad spectrum of antitumor properties. For instance, Colossolactone H (colo H), a new compound isolated from Ganoderma, was found to halt cell growth and induce cell apoptosis via the elevation of cellular reactive oxygen species to cause DNA damage and the increase of tumor suppressor p53 protein. And additional research indicated that combination of colo H and chemodrug gefitinib could effectively inhibit the growth of gefitinib-resistant H1650 lung cancer cells [1]. Moreover, lucidumol C, another new compound isolated from Ganoderma lingzhi, was found potent selective cytotoxicity against HCT-116, Caco-2, HepG2 and HeLa cell lines [2]. Ganoderenic acid B is a lanostane-type triterpene isolated from Ganoderma lucidum. It can enhance the cytotoxicity of chemotherapeutics towards ABCB1-mediated MDR cancer cells via inhibition of the transport function of ABCB1 [3].
In this project, we want to look into potential anti-cancer effect and reversal effect towards drug resistance of American Ganoderma lucidum to see if there is any difference between Ganoderma lucidum from America and China. Since this is just a preliminary research on American Ganoderma lucidum, we would utilize its crude extract to investigate the antitumor effect rather than specific compounds isolated from lingzhi.
- Problems to be solved (要解决的问题)
Through this project, we would like to determine the antitumor effect of American Ganoderma lucidum and help promote the development of dietary care strategy for cancer worldwide if lingzhi in the US could have as significant anti-cancer activity as Chinese lingzhi. And this research could also help build good foundation for further study in isolating effective compounds for cancer therapy and investigating relationship between multidrug resistance and Na, K-ATPase.
Since there have been many researches on Chinese Ganoderma lucidumrsquo;s antitumor activity so far, and many compounds have been isolated from it to investigate the potential to treat cancer, we put forward this project to see if there is also anti-cancer effect in American Ganoderma lucidum based on them.
In this project, we should first try to obtain the crude extract of Ganoderma lucidum and isolate the crude extract into four different samples according to polarity: water soluble fraction, 1-butyl alcohol soluble fraction, ethyl acetate soluble fraction and petroleum ether soluble fraction [4]. We would like to know which fraction is the most efficient part in inhibiting cancer cells growth and reversing drug resistance towards chemotherapeutic drugs such as doxorubicin (DOX) and paclitaxel (PTX). In order to compare all these four samplesrsquo; antitumor activity in vitro, we should then utilize MTT assay to determine different kinds of cancer cells growth condition under the impact of these four samples.
- Feasibility analysis (可行性分析)
Our project could be done under the guidance of our instructors--Dr. Zijian Xie and Dr. Renwang Jiang. Dr. Xie is the director of Marshall Institute for Interdisciplinary Research. On one hand, he is the professor of physiology, pharmacology and medicine who earned a bachelorrsquo;s degree from the Nanjing College of Pharmacy in Nanjing, China, in 1982, a masterrsquo;s degree in toxicology at the Chinese Academy of Medical Sciences in Beijing in 1984 and a doctorate in pharmacology at the Medical College of Ohio (now University of Toledo) in 1990. His rich experience in this field could help me resolve some possible problems which could happen in my future research. And he could also help me build up rigorous thoughts when completing my project.
On the other hand, his laboratory is internationally recognized for its groundbreaking work to understand the behavior of cellular pathways and their relationship to cancer and many other diseases. So the atmosphere in his lab is very suitable for me to do my research on cancer. And I could easily get access to advanced experimental equipments, the literature and up-to-date information in this field. He also holds international patents and patent applications on seven medical inventions resulting from his research. He has served as principal investigator, project leader or co-investigator on National Institutes of Health-funded projects totaling more than $10 million, and has established active international collaborations with total funding of more than $1 million. He has been involved with the creation of two spin-off companies from his research. So his research funding is very sufficient for me to complete my work, and I believe my research on American lingzhi could be promoted by him and promisingly become a kind of medicine or dietary supplement for practical use in cancer therapy.
Dr. Jiang is another famous professor who would help me accomplish my graduation project. He comes from Jinan University in China. And he has great knowledge in chemistry. He could give me guidance in extraction of traditional Chinese medicine.
In all, all the external conditions are well established for me in Marshall Institute for Interdisciplinary Research. The primary challenge will be the operatorrsquo;s operation, which might lead to inconsistent experiment results. But I think after several times of practice, I could master all the experimental skills necessary in my project, such as cell culture and animal study.
- Methods and contents of research (研究方法和内容)
MTT assay:
Measurement of cell viability and proliferation forms the basis for numerous in vitro assays of a cell populationrsquo;s response to external factors. The reduction of tetrazolium salts is now widely accepted as a reliable way to examine cell proliferation. The yellow tetrazolium MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) is reduced by metabolically active cells, in part by the action of dehydrogenase enzymes, to generate reducing equivalents such as NADH and NADPH. The resulting intracellular purple formazan can be solubilized and quantified by spectrophotometric means.
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