RESUMO
We investigated the methylation state of the epidermal growth factor receptor (EGFR) gene promoter in non-small cell lung cancer (NSCLC) and analyzed its effect on tumor biology. We enrolled 120 patients with NSCLC who had been confirmed by pathologic diagnosis and had been operated on. The methylation states of the EGFR gene promoter were detected and analyzed and a prognosis was given. NSCLC cell lines and nude mice were used to study the treatment reactivity of gefitinib (an EGFR inhibitor) with or without 5-aza-2'-deoxycytidine (5-aza-CdR) intervention. EGFR expression was high when the methylation degree was lower in patients with adenocarcinoma and poor pathological differentiation of tumor than in patients with squamous cell carcinoma and good pathological differentiation. NSCLC cells with low expression of EGFR and high methylation in the promoter region were insensitive to EGFR-targeted therapy. However, apoptosis and proliferation inhibition of cancer cells were even more pronounced when 5-aza-CdR was used to inhibit methylation. An in vivo study confirmed that methylation adjuvant therapy can improve the sensitivity of cancer to EGFR-targeted therapy. Application of a demethylating agent could be an important supplement for improving EGFR inhibition in the treatment of NSCLC, especially in those who are insensitive to the use of an EGFR inhibitor alone.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Animais , Antineoplásicos/farmacologia , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To study the effect and mechanism of Kidney tonifying and blood circulation activating Chinese drugs (KB) on development of mammary gland. METHODS: Using the female juvenile rats as the experimental targets, the level of serum hormone, the amount and affinity of estradiol receptor (ER) and progesterone receptor (PR) as well as the DNA content and relative weight of the rats' mammary glands were measured to study the effect of KB at the pre-receptor, receptor and post-receptor level. RESULTS: KB markedly enhanced the serum level of estradiol, progesterone and the growth hormone (GH) at pre-receptor level, increased the number and affinity of estradiol and progesterone receptors both in the cytoplasm and nucleus at the receptor level. While at the level of post-receptor, it increased the DNA content and the weight index of mammary glands. CONCLUSION: The Kidney tonifying and blood circulation activating Chinese drugs are effective in promoting the growth and development of mammary glands.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Receptores de Estradiol/metabolismo , Receptores de Progesterona/metabolismo , Animais , Combinação de Medicamentos , Estradiol/sangue , Feminino , Glândulas Mamárias Animais/metabolismo , Progesterona/sangue , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
OBJECTIVE: To study the effects and mechanism of Kidney reinforcing and blood circulation activating Chinese medicine (K&B) on morphologic structure of mammary glands in female rat models of mammary atrophy and mammary hyperplasia. METHODS: The models of mammary gland atrophy and hyperplasia were established respectively by ovariectomy and diethylstilbestrol injection to observe the changes of gland's weight index, structure, estradiol receptor (ER) and progesterone receptor (PR) after treated by K&B. RESULTS: (1) K&B could ameliorate the atrophied structure of mammary gland with significant increase of weight index (P < 0.01), raise the number of ER and PR in mammary tissue and nuclei (P < 0.01, P < 0.05), normalize the ratios of ER and PR in plasma and those in nucleus (EnR/EcR and PnR/PcR). (2) K&B could also improve or restore the proliferated structure of mammary gland and its weight index as well as the EnR/EcR and PnR/PcR ratios. CONCLUSION: K&B has the effects in preventing and improving the mammary gland atrophy induced by hyposecretion of sexual hormone and promoting the development of mammary gland in adult rats. Although both K&B and estrogen can improve the development of mammary gland, their mechanisms are different. There is a bright future of K&B in treating underdevelopment of mammary gland.
