Drug Resistance, Neoplasm ; Humans ; Multiple Myeloma

The study was aimed to investigate the effect of quercetin, flavonoid molecules on reversing leukemia multidrug resistance and its mechanism. K562/A cells were cultured in vitro with different concentrations of quercetin. Cell growth inhibition and adriamycin (ADR) sensitivity were detected by MTT method. Intracellular ADR concentration was determined by flow cytometry. Cell apoptosis was assayed by Annexin V/PI staining method. The expressions of drug transporter and apoptosis related genes were measured by real-time PCR array. The results indicated that quercetin inhibited the proliferation of K562 and K562/A in 5-160 µmol/L and with dose-dependent manner. Quercetin increased the sensitivity of K562/A cells to ADR in a low toxicity concentration. Flow cytometry showed that the quercetin increased the accumulation of ADR in K562/A cells when cells were co-cultured with 5 µmol/L ADR for 2 hours. Quercetin could induce the apoptosis of K562 and K562/A cells with dose dependent manner. Furthermore, some drug transport related genes such as ATP-binding cassette (ABC) and solute carrier (SLC) and some apoptosis-related genes such as BCL-2, tumor necrosis factor (TNF), tumor necrosis factor receptor (TNFR) families were down-regulated by quercetin. It is concluded that quercetin reverses MDR of leukemic cells by multiple mechanisms and the reversing effect is positively related to drug concentration.
Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; K562 Cells ; Quercetin ; pharmacology

Drug therapy is one of the efficient methods for prostate cancer treatment. However, drug resistance greatly hindered the treatment of prostate cancer patients. Herein, the mechanisms of drug resistance in prostate cancer have been exhaustively reviewed, and that can provide an alternative strategy and new targets for anti-prostate cancer therapy.
Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms ; drug therapy

Drug Resistance, Neoplasm ; Humans ; Stomach Neoplasms ; drug therapy

Major progress in the management of osteosarcoma has been made due to advances in diagnostic imaging, operative technique, and chemotherapy, resulting in an improved survival. However, 20~30% of patients with osteosarcoma still develop distant metastases despite combined modality treatment. Currently various experimental efforts are being proposed to the future new strategy include drug resistance, suppression of metastasis mechanism, and targeted therapy to convert the incurable rate of 20~30% upto complete cure rate.
Diagnostic Imaging ; Drug Resistance ; Drug Therapy ; Humans ; Neoplasm Metastasis ; Osteosarcoma*

Non-Hodgkin's lymphoma (NHL) is a malignant tumor originated in lymphatic hematopoietic tissue. At present, chemotherapy is the main treatment method of NHL, but the chemoresistance is still an important reason for NHL treatment failure. The mechanism of NHL multidrug resistance (MDR) is complex, involving a variety of singnal pathways, in which mutation in the genetic level of the key genes can result in tumor cell resistance phenomenon. MicroRNA are small non-coding RNA that can be widely detected in plants,animal species and viruses. They regulate protein expression by repressing translation mRNA target at the post-transcriptional level, participating in the differentiation and development of tumor cells, as well as the occurrence and development of tumor, the change of the expression level microRNA plays an important role in the genesis and chemoresistance mechanism of NHL. Therefore, the intervening factitiously the expression level of microRNA in NHL through manufacturing antisense oligonucleotide (AMO) or using substitution of microRNA, changing the expression level of their target protein, and combining with the therapy of NHL, there will be an guiding significance in reversing the drug and radiation resistance of NHL, thus improving its poor prognosis. This article reviews the microRNAs closely related with drug and radiation resistance of NHL, and their potential targets. Furthermore, the specific role of these microRNAs in the genesis and chemoresistance mechanism of NHL are deeply elaborated.
Animals ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Lymphoma, Non-Hodgkin ; drug therapy ; genetics ; MicroRNAs ; genetics

Gastric cancer is one of the most common human malignancies and the third cause of death from cancer in China and worldwide. Chemotherapy is still one of the major treatment options for advanced gastric cancer. However,the efficacy of chemotherapy for gastric cancer remains poor due to its insensitivity and the development of multidrug resistance (MDR). While many molecules and mechanisms have been found to be associated with the development of gastric cancer MDR,the specific mechanisms remains unclear. In our current article,we reviews the identification of MDR-related molecules and mechanisms,with an attempt to a better understand the specific mechanisms of gastric cancer MDR and thus provide new insights into the fight against gastric cancer MDR.
Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Stomach Neoplasms ; drug therapy

OBJECTIVETo study the inhibitory effect of serum containing Fuzheng Jiedu decoction on leukemia multi-drug-resistance K562/A02 cells and its possible mechanism.

METHODSThe MTT method was used to detect the inhibitory rate of K562/AO2 cells treated with serum containing Fuzheng Jiedu decoction; the flow cytometry was used to detect the inhibitory effect of serum containing medicin on growth of K562/AO2 cells and P-gp expression; the Q-PCR was used to assay the BCL-2 mRNA expression; the Western blot was used to detect the BCL-2 protein expression.

RESULTSMTT cytotoxic test showed serum containing Fuzheng Jiedu decoction could inhibit K562/A02 cell growth, and the inhibitory rate increased with the increase of drug concentration; the flow cytometry showed that the serum containing Fuzheng Jiedu decoction could promote K562/A02 cell apoptosis in a concentration-dependent manner. qPCR and Western blot showed that serum containing Fuzheng Jiedu decoction could down-regulate the protein expression of BCL-2. Fuzheng Jiedu decoction could reduce the protein expression of P-gp on the K562/A02 cell membrane.

CONCLUSIONserum containing Fuzheng Jiedu decoction can promote K562/A02 cell apoptosis, its mechanism of inducing apoptosis may be related with the inhibition of BCL-2 and P-gp protein expression.

Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Medicine, Chinese Traditional ; methods ; Neoplasms

This study was aimed to investigate the effects of low frequency and power ultrasound combined with adriamycin on apoptosis of drug-resistant leukemia cell line K562/A02 in vitro, to find out the parameters of optimal exposure, and to explore the possible mechanism reversing drug-resistance of K562/A02 cells. The K562/A02 cells in logarithmic growth phase were used in experiments. The experiments were divided into 4 groups: group control, group adriamycin (A02) alone, group ultrasound (US) alone and group A02+US. The trypan blue dye exclusion test and MTT assay were used to determine the cell viability; Wright's staining was used to detect the apoptosis; the flow cytometry was used to analyze the drug concentration, and the scanning electron microscopy was used to observe the changes of cell surface. The results showed that the significant differences in cell viability, intracellular adriamycin concentration and changes of cell membrane were found between ultrasound-treated and untreated cells in the presence of various concentration of adriamycin. The exposure to ultrasound at 20 kHZ, 0.25 W/cm2 for 60 seconds could obviously decrease LC50 of adriamycin to K562/A02 cells, while the exposure to ultrasound at 20 kHZ, 0.05 W/cm2 for 60 seconds could kill K562/A02 cells at once. After being treated by low frequency ultrasound, the small holes with diameter about 1-2 microm in the cell surface appeared. The ultrasound increased the adriamycin concentration in the cells, accelerated the formation of apoptotic bodies, and promoted apoptosis of adriamycin-resistant cells. It is concluded that the ultrasound at optimal parameters enhances inhibitory effect of adriamycin on drug-resistant cell line, thereby reverses drug-resistance of drug-resistant cell line through sound-hole effect in tumor cells resulting from ultrasound induced cavitation.
Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; K562 Cells ; Ultrasonics