The Study Of Lung Cancer On Pathogenesis And Treatment Based On Cold Syndrome Of TCM

The causes of cancer remained controversial.The modern traditional Chinese medicine was generally believed that tumor was hot poison based on the strong anti-tumor effect of cold drugs in vitro.So large dose of cold Chinese medicine was used in the cancer clinical treatment.This treatment ignored the traditional Chinese medicine treatment principle of "cold damage stomach, serious illness cure slowly" Although it showed curative effect in the initial term,the long-term effect was not ideal. Most patients condition changed for the worse by Yang Qi loss and Stomach Qi damage.This study concentrated on lung cancer and found the neglected tumor etiology and pathogenesis of “cold induced accumulation",“long time accumulation made tumor” by re-examining the pathogenesis and therapeutic principles of cancer which is now generally approved and actively exploring the ancient medicine. And it was hypothesized that hot Chinese medicine could turn over negative to positive, prevent tumor poison invagination in the role of lung cancer treatment.To verify the theory of "tumor caused by cold",malignant transformation of bronchial epithelial cells(BEAS-2B)induced by MNU was used to investigate the effects of low temperature on malignant transformation and explore its possible mechanism in this study.And we compared the therapeutic effect of hot medicine Aconiti Kusnezoffii Radix and cold medicine Coptidis Rhizoma on Lewis lung cancer in vivo and vitro by exploring the effect of the two on tumor bearing mice cold-coagulation blood-stasis TCM symptoms, tumor cell GJIC and tumor cell differentiation to assist to proof the theory of "tumor caused by cold".The results of this study showed that, low temperature could reduce the DNA damage of MNU treated BEAS-2B cells,promote proliferation, reduce apoptosis, promote the clone formation,and ultimately promote normal cell deterioration. When supported it by the effects of Aconiti Kusnezoffii Radix and Rhizoma Coptidis on lung cancer,we found that Aconiti Kusnezoffii Radix could inhibit tumor growth and metastasis in vivo, reduce capillary permeability and the expression of HIF-1α, improve hypoxia intra tumor and lung and GJIC, maintain body temperature significantly,improve the autonomic activity and blood oxygen saturation and increase red cell ATPase activity and blood rheology in tumor bearing mice. Although it could inhibit tumor growth,Rhizoma Coptidis promoted tumor metastasis, increase hypoxia intra tumor and lung and capillary permeability, spoil the GJIC,and aggravate the mouse physiological condition of cold-coagulation blood-stasis. In vitro experiments, rat serum containing aconite under experimental concentration could inhibit the proliferation and adhesion very significantly( P<0.01),increase the activity of SDH and decrease the positive expression of MUC1 in lewis cells, which showed strong inducement of cell differentiation,and the inducement of differentiation was stronger with the increase of concentration.Although the rat serum containing Rhizoma Coptidis could inhibit cell proliferation,it could significantly promote cell adhesion, inhibit the activity of SDH and GJIC and improve the MUC1 positive ratio at the relative concentration of 1/40,which showed no inducing differentiation effect.The mechanism exploration experimental results showed that, low temperature could reduce the secretion of TNF- α and increase the secretion of TGF-β1in BEAS-2B transformed cells. Neutralization of TNF- α could promote the transformed cells proliferation,and neutralization of TGF-β1 could inhibit proliferation, but both decreased the ability to form clones.The malignant transformation of normal cell was affected by the balance between TNF- α and TGF-β1expression.Compared with37 ℃, low temperature of 28 ℃enhanced the EMT and reduced the toxicity of CTL to A549 significantly.Further study found that EMT induced by MNU depended on the expression of TGF-β1.Although TGF-β1 could reduce the toxicity of CTL, low temperature reducing the toxicity of CTL was not entirely dependent on the expression of TGF-β1, which suggesting that the effect of low temperature on EMT was only partially dependent on TGF-β1,there may be other mechanisms.In summary, the low temperature could promote MNU treated BEAS-2B cells deteriorating by adjusting the TGF-β1and TNF- α expression balance, promoting EMT, reducing mice CTL toxicity.Hot medicine can improve symptoms of cold coagulation and blood stasis in tumor bearing mice,promoted GJIC and induced tumor cell differentiation to achieve to turn negative to positive and stop the poison invagination,which is more conducive to the treatment of tumor than cold Chinese medicine.