HUMAN COLON-CANCER;
GUT MICROBIOTA;
ACQUISITION;
MECHANISMS;
METFORMIN;
OUTCOMES;
STRESS;
ARREST;
PCR;
D O I:
10.1155/2022/6565300
中图分类号:
Q81 [生物工程学(生物技术)];
Q93 [微生物学];
学科分类号:
071005 ;
0836 ;
090102 ;
100705 ;
摘要:
Colorectal cancer (CRC) is the third most common cancer worldwide. The gut microbiota plays a critical role in homeostasis and carcinogenesis. Butyrate, a short-chain fatty acid produced by the gut microbiota, plays a role in intestinal homeostasis and acts as an anticancer agent by inhibiting growth and inducing apoptosis. However, microbiota studies have revealed an abnormally high abundance of butyrate-producing bacteria in patients with CRC and indicated that it leads to chemoresistance. We characterized butyrate resistance in HCT-116 and PMF-K014 CRC cells after treatment with a maximum butyrate concentration of 3.2 mM. The 50% inhibitory concentration of butyrate was increased in butyrate-resistant (BR) cells compared with that in parental (PT) cells. The mechanism of butyrate resistance was initially investigated by determining the expression of butyrate influx- and drug efflux-related genes. We found the increased expression of influx- and efflux-related genes in BR cells compared with that in PT cells. Proteomic data showed both identical and different proteins in PT and BR cells. Further analysis revealed the crossresistance of HCT-116 cells to metformin and oxaliplatin and that of PMF-K014 cells to 5-fluorouracil. Our findings suggest that the acquisition of butyrate resistance induces the development of chemoresistance in CRC cells, which may play an important role in CRC development, treatment, and metastasis.
机构:
Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R ChinaChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
Xu, Ling-Wen
Zhang, Xue-Qian
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Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R ChinaChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
Zhang, Xue-Qian
Yan, Zheng
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Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R ChinaChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
Yan, Zheng
Li, Zhi-Hong
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Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R ChinaChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
Li, Zhi-Hong
Deng, An-Jun
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Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R ChinaChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
Deng, An-Jun
Qin, Hai-Lin
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Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R ChinaChinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
机构:
Kyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Yoshiyama, Akira
Morii, Takeshi
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Kyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Morii, Takeshi
Ohtsuka, Kouki
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机构:
Kyorin Univ, Fac Med, Dept Clin Lab Med, Mitaka, Tokyo, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Ohtsuka, Kouki
Ohnishi, Hiroaki
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机构:
Kyorin Univ, Fac Med, Dept Clin Lab Med, Mitaka, Tokyo, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Ohnishi, Hiroaki
Tajima, Takashi
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Kyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Natl Canc Res Ctr, Res Inst, Dept Drug Design Proteome Area Res, Chuuo Ku, Tokyo, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Tajima, Takashi
Aoyagi, Takayuki
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Kyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Aoyagi, Takayuki
Mochizuki, Kazuo
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机构:
Kyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Mochizuki, Kazuo
Satomi, Kazuhiko
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Kyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
Satomi, Kazuhiko
Ichimura, Shoichi
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Kyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, JapanKyorin Univ, Fac Med, Dept Orthopaed Surg, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan
机构:
Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, NetherlandsSVERIs Coll Pharm, Ctr Drug Design & Discovery, Pandharpur, India
Peters, G. J.
Lemos, Clara
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机构:
Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands
Univ Porto, Fac Med, Dept Biochem FCT U38, P-4200319 Oporto, PortugalSVERIs Coll Pharm, Ctr Drug Design & Discovery, Pandharpur, India
Lemos, Clara
Kathmann, Ietje
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机构:
Univ Porto, Fac Med, Dept Biochem FCT U38, P-4200319 Oporto, PortugalSVERIs Coll Pharm, Ctr Drug Design & Discovery, Pandharpur, India
Kathmann, Ietje
Mayur, Y. C.
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机构:
SVERIs Coll Pharm, Ctr Drug Design & Discovery, Pandharpur, India
Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, NetherlandsSVERIs Coll Pharm, Ctr Drug Design & Discovery, Pandharpur, India