November 8, 2020/Medical College, Tibet University/Pharmaceutical Biology
Text/Wu Tingyao
Can cancer patients take Ganoderma lucidum while receiving targeted therapy? Hope the following research report can provide some answers.
Gefitinib (GEF) is one of the most important target drugs for the treatment of advanced and metastatic non-small cell lung cancer (including lung adenocarcinoma, squamous cell lung cancer, and large cell lung cancer), bringing a glimmer of hope to patients who are surviving in the dark. But the light at the exit of the tunnel may not always be on, because drug resistance tends to develop after ten to sixteen months of treatment.
Therefore, if we can seize the time to improve the curative effect of GEF, try to treat lung cancer to a more controllable and better-maintained state or even reduce the side effects of drugs so that patients can have a better physical condition to deal with cancer, maybe there is an opportunity to make the light of life shine brighter and brighter.
Researchers from the Oncology Department of Yantai Hospital of Traditional Chinese Medicine and the Medical College of Tibet University jointly published a research report in “Pharmaceutical Biology” at the end of 2020 which proved through animal experiments that for the most common lung adenocarcinoma in non-small cell lung cancer, the combined use of Ganoderma lucidum triterpenoids (GLTs) and GEF can more effectively inhibit tumor growth and reduce the side effects of drugs, providing a new plan worth considering for related treatment strategies.
The researchers first implanted human alveolar adenocarcinoma cell lines (A549 cell lines) under the skin of mice with compromised immune systems. After the diameters of the subcutaneous tumors were approximately 6-8 mm, they began to feed Ganoderma lucidum triterpenoids (GLT, 1 g/kg/day), gefitinib (GEF, 15 mg/kg/day) or a combination of both for 14 days, and the experiment ended on the 15th day. It turned out that:
(1) Improve tumor growth inhibition rate
GLTs and GEF can inhibit the growth of lung adenocarcinoma tumors, but the combination of the two has a better effect (Figure 1~3).
Figure 1 Tumors taken out of lung adenocarcinoma mice at the end of the experiment
Figure 2 Changes in tumor growth of lung adenocarcinoma mice during the experiment
Figure 3 Tumor growth inhibition rate of lung adenocarcinoma mice by different treatment methods
2) Strengthen the inhibition of tumor angiogenesis and the promotion of cancer cell apoptosis
Tumors need to create new vessels in order to continue to grow. Therefore, the density of microvessels in tumor tissues has become an important key to the smooth growth of tumors. Figure 4 (A) shows the distribution of microvessels in the tumor tissue slices of each group. Figure 4 (B) indicates that the combination of GLTs and GEF has a better inhibitory effect than the two alone.
Figure 4 Tumor tissue sections and microvessel density of lung adenocarcinoma mice
In other words, the combination of GLTs and GEF can block more tumor tissues from obtaining nutrients and make tumors more difficult to grow. This mechanism of action comes from the strengthened regulation of related gene expression and protein secretion in tumor tissues, including inhibiting the “vascular endothelial growth factor receptor 2 (VEGFR2)” and promoting the production of “Angiostatin” and “endostatin”.
In addition, the researchers also observed in the tumor tissue sections of each group of mice that under the combined action of GLTs and GEF, the secretion of protein (Bax) that promotes cancer cell apoptosis will significantly increase while the secretion of protein (Bcl-2) that inhibits apoptosis of cancer cells will decrease. The lung adenocarcinoma cells accelerate in developing towards the direction of apoptosis in this plus and minus force.
(3) Reduce the side effects of drugs
Lung adenocarcinoma mice that was only treated with GEF had the most weight loss; on the other hand, the combination of GLTs and GEF can best maintain the bodyweight of lung adenocarcinoma mice ── closest to that of normal mice (normal control group) (Figure 5).
In addition, lung adenocarcinoma mice only treated with GEF showed anxiety, fatigue, sleepiness, decreased activity, reduced appetite and dull skin. However, these conditions were much lighter or not obvious in the group treated with the combination of GLTs and GEF. Obviously, GLTs can correct the adverse side effects caused by GEF.
Figure 5 Curves of weight records and changes in lung adenocarcinoma mice during the experiment
(4) The safety of GLTs
In order to evaluate the safety of GLTs, the researchers cultured normal human alveolar epithelial cell lines BEAS-2B and human alveolar adenocarcinoma cell lines A549 used in animal experiments respectively with GLTs in vitro for 48 hours.
The results are shown in Figure 6. When the GLTs (concentrations of 2.5 and 5 mg/L) inhibited the survival rate of lung adenocarcinoma cells to 80-60%, normal cells were still alive; even at high concentrations, GLTs still clearly treat cancer cells and normal cells differently, and this distinction is even more significant than GEF (Figure 7).
Figure 6 The inhibitory effect of GLTs on cell growth
Figure 7 The inhibitory effect of gefitinib on cell growth
According to the researcher’s analysis,the IC50 values of GLTs at 48 h of treatment for the A549 cell lines was 14.38 ± 0.29 mg/L while GLTs showed a much less potent cytotoxic effect on the BEAS-2B cell line with an IC50 value of 78.62 ± 2.53 mg/L, which means that when the GLTs are lethal to cancer cells, they can still maintain a high degree of safety to normal cells.
GLTs and targeted therapy go hand in hand, making the treatment more promising.
This research report has shown us:
Under the same experimental conditions, oral administration of GLTs may not have the same inhibitory effect on human lung adenocarcinoma tumors as GEF, but GLTs have no side effects of GEF.
When GLTs and GEF work together, they can not only increase the inhibitory effect on tumor growth but also reduce gefitinib’s effects on weight, spirit, vitality, appetite and skin. This is the so-called “increasing efficiency and reducing toxicity”.
The reason why GLTs can improve GEF’s inhibition of lung adenocarcinoma tumors is related to “inhibiting tumor angiogenesis” and “promoting cancer cell apoptosis”.
In order to evaluate human cancer in animals, the researchers used mice with defective immune systems (so that human cancer cells can grow on different species). Therefore, the results were basically the effect of GLTs and GEF itself on cancer cells.
However, in the actual application of anti-cancer, the function of the immune system must be involved. Therefore, in addition to GLTs and GEF, if “good immunity” is added, will the results be more eye-catching?
The researchers did not give much description of the GLTs used in the experiment, but according to the description of the paper, it should be a crude extract of a variety of GLTs. But the effective dose of one gram per kilogram of body weight in mice is actually quite a lot. This tells us that practical applications may require a considerable dose to be effective. On the other hand, it also gives us hope that in the future it may be possible to find key ingredients that can work as well or better at lower doses.
In any case, at least this research has shown that the triterpenoids from Ganoderma lucidum not only do not hinder the treatment of commonly used clinical target drugs but also have a good effect of “increasing efficiency and reducing toxicity” based on considerable safety.
Groping in the dark tunnel requires more candlelight to lead the way and illuminate. Compared with those “hopes” that are out of reach or difficult to mass-produce, or “secret recipes” with unknown sources and ingredients, Ganoderma lucidum triterpenoids, which can be obtained as long as you want and have accumulated long-term consumption experience, should be more worth trying.
[Source] Wei Liu, et al. Ganoderma triterpenoids attenuate tumour angiogenesis in lung cancer tumour-bearing nude mice. Pharm Biol. 2020: 58(1): 1061-1068.
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About the author/ Ms. Wu Tingyao
Wu Tingyao has been reporting on first-hand Ganoderma information since 1999. She is the author of Healing with Ganoderma (published in The People’s Medical Publishing House in April 2017).
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★ The original text of this article was written in Chinese by Wu Tingyao and translated into English by Alfred Liu. If there is any discrepancy between the translation (English) and the original (Chinese), the original Chinese shall prevail. If readers have any questions, please contact the original author, Ms. Wu Tingyao.
